Phototherapy system and process including dynamic LED driver with programmable waveform

ABSTRACT

A phototherapy or photobiomodulation process employing the application of electromagnetic radiation (EMR) to a living organism, typically a human being. The EMR is generated by one or more strings of LEDs and is programmed to emit one or more wavelengths, typically in the visible and infrared portions of the spectrum, the EMR in each wavelength being delivered in pulses having specified on-times, off-times, photoexcitation frequencies, duty factors, phase delays, and power amplitudes. A system for providing such EMR includes a microcontroller having a pattern library of algorithms, each of which defines a particular sequence of synthesized pulses, and an application pad, preferably flexible, containing the LED strings.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the priority of Provisional Application No.61/723,950, filed Nov. 8, 2012, which is incorporated herein byreference in its entirety.

SCOPE OF INVENTION

This invention relates to biotechnology for medical applications,including photobiomodulation and phototherapy.

BACKGROUND OF INVENTION

Introduction

It is well known that electromagnetic radiation, a fundamental energypermeating the entire universe, affects living organisms in a widevariety of ways. Depending on the frequency or wavelength of theradiation and on its intensity or power level, electromagneticradiation, also known as EMR, may be beneficial or hazardous to livingcreatures.

Although radio waves and low power microwaves used in cell phones arelargely considered benign, deep UV (ultraviolet light) and x-rays areknown to be carcinogenetic and potentially life threatening to livingcreatures even at moderate doses. Still other frequencies, such asvisible light, are beneficial and necessary to organisms, helping powerearth's biosphere by enabling photosynthesis in plants and bacteria atthe base of our planetary food chain. EMR has also become anindispensible tool used in radio frequency and microwave communication,and in the infrared portion of the spectrum for imaging and nightvision. Unwanted electromagnetic radiation is often referred to as EMIor electromagnetic interference.

In electronics, meeting government established standards for theemission of electromagnetic noise and avoiding unwanted interferencewith other electrical devices is referred to as EMC, or electromagneticcompatibility. Other government standards apply to the maximum acceptedpower level emitted by a device (e.g. the brightness of a laser pointeror an industrial laser, or the maximum power level of a microwave ovenor a microwave communications tower), and especially for any apparatusinvolving ionizing radiation such as alpha particle and x-ray sources ornuclear material.

Physicists today regards EMR as a spectral continuum (collectively theelectromagnetic spectrum) describing a single type of energy based onthe electromagnetic force in nature, varying by its frequency(alternatively by its wave length or wave number) and by its brightness,flux density or intensity. The electromagnetic spectrum 1 shown in FIG.1 described (from left to right) in bands of decreasing wavelength (andincreasing frequency) includes AC power distribution at the longestwavelengths (not shown), followed by radio, microwave, infrared, visiblelight, ultraviolet, x-rays, gamma-rays, and beyond that, cosmic rays(not shown).

Of particular importance to humans, the visible spectrum of light (orvisible band 3) ranges from 750 nm to 400 nm varying monotonically incolor from red to orange, yellow, green, blue, and to purple (as seen ina rainbow). The combination of these colors produces white lightespecially important for color vision. Visible light is also importantin plants and algae for powering photosynthesis. Chloroplasts,organelles within plant cells, use chlorophyll to capture sunlight andto convert it into energy using the process of photosynthesis. Since thechlorophyll absorbs red, blue, and violet light, it makes plants appeargreen in color.

Light wavelengths in the band adjacent to visible light longer than 750nm and shorter than 1 mm are referred to as the infrared band 2, withthose closest to visible light referred to as “near” infrared or NIR andlonger wavelengths as long infrared and far infrared. Long infraredlight in the 8- to 15-μm range is used for infrared imaging 6 in medicaland security applications.

Light wavelengths in the adjacent band shorter than 400 nm and longerthan 10 nm are referred to as the ultraviolet band 4 with those closestto visible light referred to as near UV and the shortest wavelengths inthe hand as extreme UV or deep UV. Just beyond the ultraviolet band, theX-ray band 5 comprises soft X-rays down to wavelengths of 0.1 nm andhard X-rays beyond that. Soft X-rays are used in security applications 7for cargo and passenger inspection while shorter wavelength X-rays areused in X-ray crystallography, in radiography 8, and in computerizedtomography or CT scans.

All EMR is the propagation of energy through space and in matterachieved through a time-varying electric field and a correspondingcomplementary magnetic field created through the movement or vibrationof charged particles. Since the time-varying electric field induces acorresponding time-varying magnetic field, and conversely thetime-varying magnetic field induces an electric field, EMR can travelwithout any medium, even in the vacuum of space. Its ability topenetrate matter depends on the absorption and scattering properties ofthe matter at each particular EMR wavelength.

Traveling in space or in matter, EMR is able to manifest itself aseither a particle or a wave (but not both at the same time). When EMRmanifests itself as a particle it is commonly referred to as a “photon”,while when it behaves in a wavelike manner it is often referred to as“light waves”. The term “light”, then, is used in two ways—in thegeneral sense to mean any electromagnetic radiation in the spectrum, andin the specific case to mean only visible light and its spectralneighbors ultraviolet light and infrared light.

When EMR does come in contact with matter, it may be reflected, passthrough the matter or be absorbed altogether, affecting the EMR andoften changing the matter too. EMR's interaction with matter maymanifest itself with particle like behavior governed by classicalphysics (first historically in the “Compton Effect”), as a waveexhibiting any combination of classical wave-like phenomena such asreflection, refraction, or interference, or by quantum mechanicaleffects such as quantized energy band transitions, moleculartransformations, or quantum mechanical tunneling. Such interactionsbetween matter and EMR have been harnessed for a large number ofcommercial, scientific, and medical applications.

Interactions of EMR and matter have been used extensively in scientificresearch, especially in imaging and analytics. X-ray diffraction allowsfor precise analysis of crystalline morphology and even played a crucialrole in the discovery of DNA. EMR is also used extensively for medicalimaging. Today, X-rays are routinely employed in radiography 8 toidentify broken bones and dental cavities and in CT scans to identifytumors and tuberculosis. Imaging can also be performed using infraredlight 6 often to analyze tissue where X-ray analysis is inconclusive orinconvenient. Advanced research also includes new hand held IR imagingdevices that can identify carcinoma in tissue during surgery,particularly useful in identifying and removing cancerous cells in theborder tissue during a mastectomy, avoiding the need for costly delayswaiting for lab results and the repeat surgeries that result from thedelayed lab analysis.

EMR also plays an important and growing therapeutic role in medicine. Insome cases EMR is used to kill foreign or unhealthy cells while in otherexamples EMR is used to stimulate healing, promote immune response,reduce pain, and alleviate local inflammation.

Perhaps the best-known and oldest therapeutic use of EMR is radiationtherapy 9, applied primarily in the treatment of cancer. Because suchradiological protocols involve exposing a patient to ionizing radiationin the X-ray band 5, patients often suffer serious side effects fromradiation poisoning that compromise the medical benefit by lowering apatient's quality of life. The goal of radiation therapy is to achievetargeted cellular destruction of the cancerous cells without damaging orkilling a significant number of normal cells. Research continues inlocalizing the radiation to minimize the collateral damage to normalcells. In many cases, however, it is simply a matter of statistics—arace to destroy most of the cancer before the treatment kills thepatient.

Another therapeutic protocol of EMR using less energetic photons thanX-rays employs ultraviolet light 4 to remove unwanted antigens andbacteria from the skin. One common example of UV phototherapy is theanti-bacterial use of ultraviolet light 11 locally applied bydermatologists to treat skins rashes and irritations, in essence to“sunburn” whatever may be present on a patient's skin causing a rash oritching. Its use is often indicated even when the actual cause of anirritation cannot be confirmed.

In general, to destroy or otherwise inhibit the growth of mutated,pre-cancerous, cancerous, or un-normal cells requires the concentrationof EMR into a narrow bandwidth and a focused area to avoid damaginghealthy cells. Applying a focused beam to treat large areas isproblematic—especially once metastasis has commenced. Research in usingbeams of focused energy to perform targeted cellular destruction spansthe spectrum from the far infrared to hard x-rays.

EMR is also used for therapies not targeting cellular destruction, butinstead to promote natural healing processes within the body. Inthermotherapy 10, long wave infrared heating either through lamps orLEDs is used to raise a patient's body temperature to that similar totemperatures experienced from mild exercise. Research showsthermotherapy benefits patients suffering from severe cardiovasculardisease unable to exercise by improving cardiovascular flow over largeareas and volumes of the circulatory system.

Another EMR therapy, herein referred to as photo-optical stimulation 12,is used to counter depression and anxiety in people by visuallystimulating a patient's eyes with artificial colored or white light(essentially emulating sunlight or portions thereof) to enhance theirmood and provide a sense of wellbeing. Such photo-optical stimulationtreatments are especially important for residents of Polar Regions whereextended periods of darkness prevail for the majority of winter days,and where alcoholism and suicide rates greatly exceed that of thegeneral population globally. Photo-optical stimulation treatments havealso been used to counter severe jet lag and to restore and helpregulate sleeping patterns.

Photobiomodulation

Referring again to FIG. 1, phototherapy 14, the emerging medical fieldto which the apparatus of this disclosure relates, herein is broadlydefined as the therapeutic application of light to beneficially affectcells and tissue through photobiomodulation and the photoexcitation ofNo-molecules.

Photobiomodulation, the electrochemical response of cells and tissue todirect illumination by ultraviolet, visible and infrared light,represents a physical mechanism by which energy is imparted directlyinto a cell by photons to produce any number of photobiologicalresponses, including forming ATP (a molecular source of energy),accelerating intracellular and intercellular chemical reactions,stimulating DNA transcription and RNA translation (protein synthesis),increasing intracellular catalyst concentrations, and beneficiallyaffecting the cell and its host. Depending on the wavelength of theimpinging light, photobiomodulation has been observed in virtually everyliving creature on earth from bacteria to complex organisms, includinganimals, mammals, and even HOMO sapiens. Since, in many cases,photobiomodulation stimulates the formation of ATP and initiates proteinsynthesis, it means (at the right frequencies of light) photosynthesisoccurs not only in bacteria and in plants, but also in animals.

One of the early observations of photobiomodulation was reported in 1967by a researcher studying the biological effects of infrared laser lighton animals. Convinced the laser light caused cancer, the researchershaved mice then irradiated half of the population with low-levelinfrared light only to discover not only did the mice not contractcancer, but much to the researcher's surprise, the irradiated mice'shair grew back at a greatly accelerated pace.

The report was largely forgotten until later and quite accidentally)photobiomodulation was essentially re-discovered by NASA during thespace shuttle program, observing astronauts exposed to infrared lightfrom a plant grow lamp healed normally when those from prior missionsabsent the grow lamp did not heal normally. Further research identifiedmice poisoned with methanol and treated with infrared light retainedmost of their vision while the control group went completely blind. Thestudy identified methanol molecules which normally attach to theadenosine triphosphate (ATP) chemical bonding sites in the optical nerve(and essentially starve the nerve tissue for energy) are dislodged andreplaced by ATP generated by photobiomodulation of infrared light. Thesignificance of this study was its early identification of ATP and itsrole in the photobiological process.

Molecular studies on bacteria and plankton subsequently revealed thatlight (especially in the visible red and near infrared portion of thespectrum 13) is absorbed directly by a biomolecule cytochrome C oxidase(CCO). The CCO molecule acts as an intracellular battery chargerconverting adenosine monophosphate (AMP) into adenosine diphosphate(ADP), and then into adenosine triphosphate (ATP). If metaphorically.CCO is the battery charger, then ATP is a cell's battery—the batterypowering all the other electrochemical reactions within the cell itself.

Studies on mice and human patients found photobiomodulation of injuredtissue or organs resulted in cellular repair, tissue regrowth andaccelerated healing, improved immune response, reduced tissueinflammation, lower secondary infection risk, and faster recovery frominjury or illness. In human trials, patients also reported reduced painand improved health following only a few phototherapy treatments. Inpatients suffering from peripheral neuropathy, i.e. the death of nervesin limbs common in diabetes sufferers, partial recovery of their senseof touch was also noted. Numerous refereed professional journals (e.g.journal of Lasers in Medical Science) and various textbooks areavailable today summarizing the discovery of photobiomodulation and itsprospects for therapeutic treatments, i.e. for “phototherapy” [CharlesT. McGee, “Healing Energies of Heat and Light” Medipress, Coeur d'Alene,2000].

To date, photobiomodulation and its potential therapeutic effects havebeen studied for over four decades. Despite exciting, almostunbelievable early results, decades passed without doctors or scientistsfinding a practical or commercially viable means by which to bringphototherapy to market, due to limitations in understanding and more soin the technology of the day.

As shown in FIG. 1, phototherapy may be performed using eitherincoherent light 17 or by lasers 15. Initially, incoherent light fromthe sun and later from lamps was used, in part because of itsbroad-spectrum 17A and its ability to cover a large area 17B. Lampshowever were found to be unwieldy, consuming large amounts of power andproducing more heat than light. Subjects complained of overheating andresearchers suffered burns from handling the hot incandescent bulbs.Other studies especially in the USSR, focused on applying ceramicinfrared lamps adapted from industrial ovens and heaters, intophototherapy. These efforts concentrating primarily in the longwavelength portion of the spectrum include both beneficial phototherapyas well as targeted cellular destruction. Later, scientists alsoattempted treatments using gas discharge lamps ands noble gasses butwere limited by their inability to control the radiated wavelengths.

Research then turned to lasers 15 operating at much cooler temperaturesthan bulbs and beneficially producing more light than heat. At first itwas thought that coherent light would impart an added advantage inpenetration depth and treatment efficacy but it was soon discovered thatthe small spot size 16B of a laser made the treatment of large areassuch as a whole organ or large muscle problematic. Further studies alsorevealed that optical coherence was almost immediately lost fromscattering in the top layers of the skin anyway, so that deeppenetrating light was not coherent even when emanating from a coherentsource. Moreover, gas and dye lasers were costly, fragile, large, heavy,power hungry, and inconvenient to transport. Other studies revealed thattoo narrow of a frequency-spectrum 16B typical of laser light mightadversely reduce phototherapy treatment efficacy.

While the advent of the semiconductor laser diode helped lower thepotential cost of laser phototherapy, the small spot size of laserdiodes combined with a characteristically narrow bandwidth remainproblematic. Moreover, laser medical devices continue to pose apotential safety risk to both patients and clinicians and require strictcompliance with an ever-changing set of governmental regulations. Assuch, the broad scale commercial deployment of phototherapy devicesbased on the use of laser diodes still face numerous challenges.

In contrast, the recent commercial availability of relatively low-costbright LEDs offers a more promising means by which to engineer apractical phototherapy device. Unlike laser diodes, LEDs are rapidlyemerging as the preferred source of light to be employed in a virtuallyunlimited range of applications. Today LED lighting exclusively providesthe backlight and camera flash in virtually every mobile phone andsmartphone sold. LEDs also facilitate backlighting for the newestgeneration LCD HDTVs offering “green” (i.e. energy efficient) operationand enhanced image contrast. Since 2010, the LED began expanding intogeneral lighting applications including automobile headlamps, tail lampsand cabin lighting; into streetlights, and even into commercial andresidential lamps replacing inefficient incandescent bulbs andobsoleting hazardous mercury-contaminated compact fluorescent lamps(CFLs).

With its ubiquitous use driving high production volumes, the resultingeconomy of scale benefits, supplier competition, and new technologycontinue to drive LED costs lower, further enabling the LED'scompetitive advantage in the global marketplace. Moreover, the LED'sexceptional safety record prompted the United States government tofurther relax LED safety regulations, distinguishing the LED as aseparate and distinct category from lasers and laser diodes, authorizingunrestricted use provided an LED's power output does not exceed theFDA's guideline of 300 mW/cm².

LED Flashlight and Torchlights

One requirement for effective LED phototherapy is an electro-opticaldesign capable of maintaining a consistent LED current for extendedtreatment durations, e.g. at least 60 minutes or longer. Low-cost LEDdriver circuitry and designs used in flashlights, torchlights, and manyphone backlights, however, lack the necessary features and capability toadequately control LED brightness over such extended durations, or todistribute light uniformly. They also lack the ability to perform anumber of important functions useful in customizing treatments tospecific medical conditions, e.g. by modulating LED excitation to varyits operating frequency. FIG. 2, for example, illustrates a conventionallow-cost LED driver where four series connected batteries 20 a through20 d power one or more parallel strings of LEDs 26 a through 26 n witheach string comprising “m” series connected LEDs.

Counter 23 a and inverter 23 b, collectively as digital controller 23,digitally oscillate at a fixed clock frequency by repeatedly switchingMOSFETs 27 a through 27 n on and off, in turn toggling on and off LEDcurrents I_(LED1) through I_(LEDn) in the LED strings 26 a through 26 n.By varying the pulse width and corresponding duty factor D of the LEDcurrent conduction time by controller 23, strobe operation of the LEDsis able to facilitate fixed frequency PWM brightness control.

Unfortunately, a fundamental problem with the circuit as shown is thatit powers the LED strings with a voltage source, not current sources.LEDs prefer, i.e. behave better, being driven by constant currentsources. Voltage source drive cannot balance the current evenly amongthe LED strings 26 a through 26 n because the LED forward voltages donot match one another, varying stochastically with manufacturing andalso varying dynamically with operating current and brightness. Seriesballasting resistors 24 a through 24 n are included in an attempt tobalance the current more evenly among the LED strings but they still donot guarantee matching of current or LED brightness.

Unlike current source drive, using a voltage source and a resistorallows the LED currents and brightness to change with the power supplyvoltage, i.e. with the decay in the battery voltage. As shown in FIG. 3,as the battery voltage V_(batt) 30 declines, the potential differencebetween it and the LED string voltage V_(LED) 31 declines in proportion.Since the LED current in any given string is given byI _(LED)=(V _(batt) −V _(LED))/Rthen any change in V_(batt) over time will manifest itself as a timedependent change in LED brightness. When V_(batt) approaches V_(LED)during the battery's decay, the LEDs eventually turn off and cease toilluminate. LEI) strings with a higher forward voltage will dim fasterand turn off sooner than lower forward voltage strings causinginconsistent LED brightness over time and poor luminous uniformity aswell.

Returning to FIG. 2, in order to prevent flicker resulting fromswitching noise and current transients among channels, capacitors 25 athrough 25 n are added for filtering. Low dropout (LDO) linear regulator21 and filter capacitor C_(reg) 22 are also included to provide aconsistent voltage V_(driver) to supply digital controller 23 despitevariations in the output voltage V_(batt) of battery pack 20 duringdischarge and with LED current transients. While LDO 21 could also beused to power LED strings 24 a through 24 n, the extra voltage dropacross the LDO adversely affects the device by diminishing the peak LEDbrightness, increasing power dissipation, and resulting in the LEDsshutting off sooner than they would otherwise.

In the design, the maximum number of series connected LEDs “m” dependson the LED forward voltage, the battery chemistry and the resultingbattery voltage V_(batt). If battery 20 comprises a rechargeable LiIonchemistry each cell exhibits a nominal voltage of 3.6V andV_(batt)=14.4V. If red LEDs are used with a forward voltage of 1.6Veach, then “m” may be chosen for 8 or 9 LEDs. If infrared LEDs areemployed, each LED has a forward drop of 2.2V so that “m” is limited to5 or 6 series LEDs. If strings of red LEDs are alternated thestring-to-string voltage and current mismatch problem will be furtherexacerbated. The LED torchlight drive shown simply cannot accommodatesuch mismatches in voltage and current, and therefore mixing LED typesis problematic.

In consumer devices, however, alkaline batteries are far more commonthan expensive rechargeable LiIon cells. In such cases, each cell startsat approximately 1.5V but gradually decays to 1V per cell, with thebattery voltage ranging from slightly over 6V and decaying to 4V andbeyond. During the discharge, the LED brightness will decline constantlyduring use. At 4.2V, the LEDs no longer illuminate and the batteriesmust be replaced to continue use.

Attempt to regulate the LED voltage by introducing a voltage regulatorbetween battery pack 20 and the LED strings only makes the problem worsebecause the converter itself, consumes power further shortening batterylife. If the converter is another LDO similar to LDO 21, the voltagedrop across the LDO actually shortens the battery life. If an expensiveboost converter is employed producing a fixed voltage higher thanV_(batt), a new problem occurs. Since the forward drop across LEDstrings varies stochastically with manufacturing, at higher operatingvoltages and correspondingly, with a larger numbers of series connectedLEDs, variations in LED voltage can be substantial, especially duringthe entire manufacturing life span of a product.

To insure every LED string always has sufficient voltage to illuminateat specified current the fixed voltage output from a boost convertermust exceed the highest string voltage expected in the course ofmanufacturing. This design approach naturally results in a “high” supplyvoltage—one higher than needed for normal units having LED voltages nearthe statistical mean. The unused excess voltage produces heat in thedriver circuit in resistors 24 a through 24 n and in MOSFETs 27 athrough 27 n, lowering efficiency and shortening battery life. In LEDstrings having LED voltages below the mean, i.e. at the low end of thedistribution, the extra voltage can become excessive, even causingoverheating in the drive circuit. If the LED current is also varied, theproblem becomes further exacerbated because the LED string voltage isalso a function of operating current.

Mechanical design represents another significant limitation of LEDtorchlight designs. FIG. 4A illustrates an artist's conceptualization ofLED torchlight 35 typical to this genre of phototherapy products. Thetorchlight or “wand” has a handle portion and an LED portion comprisingan array of LEDs 35 a. The LED array is stiff and inflexible with theLEDs essentially coplanar mounted on a circuit board housed within wand35. Other versions embed the LEDs within a hairbrush.

The first problem of this design is the practical consideration oftreatment time. Phototherapy achieves photobiomodulation by introducinga sufficient number of photons into tissue to change theelectrochemistry of cells in the treated tissue. The maximum ratephotons can be introduced into tissue is practically limited to thehighest LED brightness to avoid skin burns and to comply with governmentregulations. Considering these aspects, minimum treatment times are inthe range of 20 minutes to 60 minutes depending on the tissue beingtreated. Times shorter than the prescribed amount are completelyineffective, analogous to plugging a phone into a battery charger foronly a couple of minutes. In such a short duration, the electrochemistryof a cell, like a battery, does not normalize and energy is not absorbedin any beneficial way.

Holding a wand on your skin in one specific place for 60 minutes withoutmoving it is just not possible. Any movement changes the treatmentconditions. As shown in the leftmost example of FIG. 4A, when LED wand35 is held above the skin at a distance, photons spread over a largearea but are primarily absorbed by the outer epithelial layers of skins,barely penetrating into the subdermal tissue 37. Slightly moving thewand 35 as in the middle graphic results in an entirely differenttherapy volume, being smaller in area and deeper in penetration. Theright most case shows close proximity treatment, illuminating a surfacearea no larger than that of the LED array 35 a but penetrating deep intosubdermal layers 37 To cover a large area at close proximity, a patientwould be required to hold the wand in a fixed position for longdurations multiple times until all the area was treated. Such anexhaustive procedure is simply not practical especially for patientssuffering duress from illness or pain. Likewise, no clinic can afford tohire a nurse to sit with a patient during the entire treatment just tohold LED wand 35 in place.

Expanding the size of wand 35 doesn't solve the area problem either.Making the LED area 35 a larger further exacerbates the issue ofachieving uniform penetration depth over large areas, especially becausemost treatment areas on a patients involve curved surfaces, e.g. a leg,arm, neck, side, etc. As shown in FIG. 4B, illuminating curved bodysurfaces with a stiff planar LED array results in a continuouslyvariation distance between LED and skin, resulting in a large variationin photon penetration depth 38. As illustrated, the portion of planarLED array closest to the skin in the center of the array will penetratedeeper than the edges.

The tighter the curvature of the treated body part, the worse theuniformity problem becomes, with arms and legs and fingers suffering thepoorest illumination uniformity.

Combining the low cost LED torchlight drive circuitry with a flat wandor flashlight illuminator shape renders such consumer orientedcompletely impractical to use and ineffectual in their result. Giventhese severe design issues, such consumer “gadgets” cannot be consideredas real phototherapeutic devices or as prior art apparatus or method forachieving photobiomodulation or delivering phototherapeutic treatments.

HDTV Backlight Drivers

State-of-the-art for the electronic drive of LED arrays today is bestexemplified by integrated circuits (IC) for LED backlighting of largeLCD (liquid crystal display) panels, especially those used in LEDbacklit HDTVs (high definition televisions). While the end application,design, operation, and software programming of these systems have beenspecifically designed and created for driving white LEDs in LED backlitHDTVs, the hardware and IC implementation of such systems is vastlybetter than the torchlight driver circuitry used in present dayphototherapy devices and consumer gadgetry.

FIG. 5A illustrates the basic elements of a LED backlit HDTV comprisinga liquid crystal display (LCD) panel 42, a color filter 43, and a LEDbacklight including an array of white LEDs 41 and LED backlight driverIC 45. TV viewers 44 observe color 2D or 3D images on the LCD panel byseeing light produced by the array of white LEDs 41 penetrating somefraction of the pixels, i.e. picture elements, in liquid crystal displaypanel 42 and passing through color filter 43. LCD panel 42 acts like anadjustable window-blind offering 256 or more “grey scale” levels oflight transmissivity ranging from black (opaque) to full brightness(transparent) and every intermediate brightness. The combination ofblack, white, and grey pixels forms two-dimensional (2D) images on thedisplay as seen simultaneously by both left and right eyes of observer44.

Transmitted light passes through color filter 43 with the light from anygiven LCD pixel passing only through one of three colors—red, green, orblue. Because white light emanating from white LED 41 contains all thecolors of the rainbow, color filter 43 is able to filter each pixel intoone color only, either red, blue or green, For example, a red colorfilter actually absorbs all the colors except red light, removing bluegreen, violet, etc., to give the light a red color.

The combination of all three colored pixels, one red, one blue and onegreen, can then be used to recreate images with virtually any color inmillions of shades and brightness levels. Such a display is referred toas a RGB color LCD. The data sent to each red, green, and blue pixel areprocessed by a video processor IC and set to a combination of row andcolumn drivers, managed by a complex digital video timing controller. Anew picture is loaded and rescanned at a fixed period known as thevertical synchronization or Vsync pulse which typically occurs a rate of60 Hz in older TV models and at 120 Hz or 240 Hz in today's newest highperformance HDTVs.

Synchronized to the LCD image and to the Vsync pulse, LED backlightdriver 45 controls the brightness of the array of white LEDs 41 usingpulse width modulation (PWM) brightness control operating a fixed clockfrequency and updated once every Vsync pulse. The backlight may beuniform in brightness operating at a single duty factor D and adjustablein brightness for the entire display. Uniform backlight brightness of anLCD backlight is referred to a global dimming control. Alternatively,the backlight may be broken into tiles or segments with each tileilluminated to the proper brightness corresponding to the image in thatportion of LCD panel 42 located directly above the backlight tile. Byvarying the LED brightness in conjunction with the image, e.g. wheredark portions of the image are illuminated by a dimmer LED backlight,power is saved and image contrast enhanced. Using local dimming, blackslook blacker, and bright images look brighter, for the first timeenabling the means for “mega-contrast” performance in LCDs comparable tothat of power hungry plasma displays.

Local dimming in LED backlit LCDs is achieved by “current control” ofLED string currents using ground-connected current sources, commonlyknown as “current sinks” as shown in FIG. 5B. These current sinks 56 athrough 56 n individually respectively control the current in LEDstrings 57 a through 57 n. Each current sink includes feedback(schematically represented by a current sense loop and analog input toeach dependent current source) to dynamically adjust gate drive of thetransistors comprising said current sink in order to maintain apreprogrammed value of sink current independent of voltage. Each currentsink 56 a through 56 n is toggled on and off by digital signals 58 athrough 58 n respectively.

These digital signals are output from LED driver circuit 55 comprisingLED driver ASIC 56 a set of digital buffers needed to drive the linecapacitance of signals 58 a through 58 n distributed across the LEDbacklight board. Switched at a fixed frequency, the digital signals 58 athrough 58 n each vary independently in duty factor D to adjust thecorresponding current and brightness of each LED string 57 a through 57n. Global dimming and overall brightness control is performed byoperating each LED string at the same duty factor D. Operating eachstring at its own unique duty factor D₁ through D_(n) performs localdimming in response to instructions received from video scalar IC 54communicating to LED driver 55 through digital SPI bus 59 a. In somecases the video scalar IC 54 communicates to a microcontroller (notshown), interpreting and in turn instructing LED driver 55 regarding theproper drive for each LED string for local dimming.

As shown, switch mode power supply 52 and filter capacitor 53 c powerall the LED strings at a regulated voltage +V_(LED). White LEDs aregenerally constructed using wide bandgap materials to produce bluelight. The blue light is subsequently converted into white light byphosphor in the LED lens. Because white LEDs employ wide bandgapmaterials, the voltage drop across white LEDs is quite high, typically3.5V to 4V per LED. This means the output of SMPS 52 is often highvoltage, ranging from 60V when in, the number of series connected LEDs,is below 15, to over 200V for larger values of m.

The voltage rating of capacitor 53 c should be scaled accordingly withits capacitance value Creg3, sufficient to stabilize the regulator'scontrol loop and adequate to support the worst-case LED transientswithout dropping out of regulation. Individual ripple filteringcapacitors on each LED string (like those shown in FIG. 2) are notneeded in this design because current sinks 56 a through 56 n maintainthe individual LED currents ILED1 through ILEDn despite fluctuations involtage arising from transient voltage drops or string-to-string voltagemismatch. In battery powered applications such as a notebook computersVin is typically in the range of 15 to 20V, SMPS 52 typically comprisesa boost converter and Vlogic and Vdriver are regulated using LDO linearregulators 50 and 51.

In monitors and HDTVs, the input voltage is typically the AC-mains,either 110 VAC or 220 VAC, and SMPS 52 is generally an isolated flybackconverter. In such cases SMPS 52 often includes a second output,typically 24 VDC or 12 VDC, sued to power LDOs 50 and 51.

As shown in FIG. 6A, PWM brightness control in 2D HDTVs if performedusing a fixed frequency clock pulse to generate a programmableduty-factor-controlled LED (output) current waveform. A microcontroller,video processor IC, or timing generator IC generates a vertical syncsignal Vsync 60 having a period T_(sync) typically corresponding to afrequency of 60 Hz, 120 Hz, or 240 Hz. The lowest of these frequencies,i.e. 60 Hz, was chosen historically to be the lowest frequency that wassufficiently fast that the human eye could not see the screen imagechange or flicker. More recently double or quadruple Vsync frequencieshave been used to reduce image blur and to facilitate 3D displays. TheVsync pulse acts as the main clock in an LCD or HDTV as it is used in avariety of functions including the instruction to load video data fromthe video processor into the LCD column drivers, to advance the LCD scanby one row, and to load information into the LED backlight drivercontrol registers.

In an LED backlit HDTV offering brightness control, a second clock 61 isgenerated and synchronized to the Vsync clock 60 but operating at ahigher frequency. For example in a HDTV offering 4096 levels or 12-bitsof dimming control, the second clock, sometimes referred to as a greyscale clock or GSK, runs at a frequency f_(θ) that is 4096 times fasterthan the Vsync pulse rate, i.e. having a grey scale clock period ofT_(θ)=Tsync/4096. By employing programmable counters in an LED driverIC, the average LED brightness can be varied from 0% to 100% in 4096steps either locally or globally, each step representing approximately0.0244% variation in backlight brightness.

This backlight brightness control and dimming feature can be implementedwithout the need to change LED conduction current. In the graph forCurrent Reference 62, the value of LED current in any channel set by theprecision Current Reference 62 remains constant at a user programmablevalue 62 a equal to I_(ref) throughout. Instead of changing currents,the duty factor D is varied dynamically to adjust backlight brightness.Referring again to FIG. 6A, the LED on-time is initially operated at anspecific on-time t_(on1) resulting in a 66% duty factor shown by curve65 a whereD ₁ =t _(on1) /T _(sync)=66%meaning during each Tsync period prior to time t₁, LED (Output) Current63 operates two-thirds of the time in an on-state 64 a conducting acurrent equal to αI_(ref) and one-third of the time 64 b in an off-stateat zero current. Described in terms of the programmable counter andClock 61 switching at frequency f_(θ)=4096/Tsync, the on-time andoff-time for 66% duty factor operation is 2730 clock pulses and 1366clock pulses respectively. The average LED current and therefore LEDbrightness shown by curve 65 a represents a level 66% that of the pulsedcurrent value αI_(ref).

Between time t₁ and time t₂, the brightness control changes to a dutyfactor of 50% as shown by average value 65 b, so thatD ₂ =t _(on2) /T _(sync)=50%and where t_(on2) digitally represents 2048 clock pulses, or half thenumber of the period's 4096 pulses. Similarly between time t₂ and timet₃, is the brightness control increases to a duty factor of 75% as shownby average value 65 c, whereD ₃ =t _(on3) /T _(sync)=75%and where t_(on3) digitally represents 3072 clock pukes, orthree-quarters of the period's 4096 pulses. After time t₃ the averageduty factor 65 d drops to only 12% or 491 pulses per period. Backlightoperation at such low duty factors typifies sleep mode operation where adisplay is dimmed dramatically to reduce power consumption, save batterylife, or improve a display's green power rating.

FIG. 6B shows the waveforms for the same display changing operation from2D mode into 3D mode. Three dimensional image display in HDTVs, alsoknown as 3D mode, involves alternately displaying two images, one forthe left eye, the other for the right eye, and switching the images at asufficiently high rate that the eye cannot see the alternating images.The left and right images are separated using glasses worn by the viewerthat only allow the left eye to see the left eye image and only allowthe right eye to see the right eye image. This may be accomplished usingpassive glasses comprising two different polarizing filters and bychanging the polarization of the display image in alternating fashion todirect the image to the corresponding eye. Alternatively, active glassescomprising LCD shutters synchronized to the display images may be usedto control which eye sees which image.

In any event, because only one eye sees the display's image at a time,the duration by which the image is displayed must be half the time ofthat in 2D mode. To avoid the perception of flicker the image must bescanned at twice the normal Vsync. For example if a HDTV normallyoperates a 60 Hz Vsync rate, then in 3D mode the display and thebacklight must operate at 120 Hz. If a HDTV normally operates at 120 Hzin 2D mode, in 3D mode the Vsync rate is doubled to 240 Hz.

As shown prior to time t₇, the Vsync pulse occurs at a fixed rate with aperiod T_(sync) for normal 2D mode operation, after which, the Vsyncrate doubles to a pulse with period T_(sync)/2. At time t₇, Grey scaleClock 61 also doubles in frequency from f_(θ) (2D mode)=4096/T_(sync) toa rate f_(θ) (2D mode)=4096/T_(sync). Although the clock rate doubles,since the programmable counter relies on the clock, the duty factorstays constant. For example, between time t₆ and time t₇, the brightnesscontrol has a duty factor of 50% as shown by average value 65 f, wherebyD ₇ =t _(on7) /T _(sync)=50%

After the frequency doubles at the onset of 3D operation, t_(on8) isreduced to half the value of t_(on7), i.e.t _(on8) =t _(on7)/2

But likewise, T_(sync3D) is reduced to T_(sync)/2 so thatD ₈ =t _(on8) /T _(sync3D)=(t _(on7)/2)/(T _(sync)/2)=D ₇=50%

So changing the Vsync frequency has no bearing on the PWM duty factor orPWM brightness, as shown by duty factor curves 65 f and 65 g. Butbecause in 3D mode only eye is seeing the display image at a time, thehuman mind perceives the brightness as half that of normal brightness.To compensate for this effect, the brightness of the LED backlight mustdoubled in 3D mode from αI_(ref) to a value of 2αI_(ref). In otherwords, the brightness of the LED pulses doubles in brightness in 3D modebut since only one eye sees them at a time, there appears to be nochange of brightness compared to 2D mode.

A TV backlight driver IC capable of performing all these operations isillustrated schematically in FIG. 7 comprising channel drivers 69 athrough 69 n and control section 69 z (collectively as LED driver 69)driving LED strings 57 a through 57 n powered by SMPS 52. In thissystem, video information from video scalar IC 54 is transferred via SPIbus 59 a to microcontroller 67. Microcontroller 67 interprets this videoinformation and passes it to the control section 69 z of LED driver IC69, specifically via SPI bus interlace 59 b. The SPI bus thendistributes the information to decoders 74 a through 74 n using digitalbus 73 which instructs the individual channel drivers on driveconditions including timing and biasing. For high speed datatransmission with a minimal number of interconnections, digital bus 73represents some combination of serial and parallel communication. Sincethe bus is dedicated to the LED driver, such a bus may conform to itsown defined standards and is not subject to complying with anypre-established protocol as SPI bus 59 a and 59 b are.

This digital information from digital bus 73, once decoded by decoders74 a through 74 n, is next passed to digital data registers, i.e. datalatches, present within each individual channel driver 69 a through 69n. In the schematic of FIG. 7, the decoded data includes a 12 bit worddefining up to 4096 increments in duty factor D, for brightness control,a 12 bit word defining up to 4096 increments in phase delay φ used tocompensate for propagation delays across a panel and to minimize powersupply inrush currents, and a 8 bit word Dot for setting the LEDcurrents used in current calibration to improve backlight uniformity(i.e. dot correction) and used to switch between 2D and 3D displaymodes.

For example, synchronous to each vertical sync pulse on Vsync line 60,decoder 74 a loads a 12-bit word into D register 75 a, a 12-bit wordinto φ register 76 a, and a 8-bit word into Dot register 77 a containedwithin individual LED drive channel 69 a. In similar fashion andsynchronous to Vsync pulse on line 60, decoder 74 b loads a 12-bit wordinto D register 75 b, a 12-bit word into phase delay φ register 76 b,and a 8-bit word into Dot register 77 b contained within individual LEDdrive channel 69 b. The same process occurs simultaneously for all nchannels, i.e. from channel drivers 69 a through 69 n.

Once the data from decoder 74 a is loaded in duty factor D register 75 aand phase delay φ register 76 a, counter 78 a begins to count pulsespresent on Clock f_(θ) line 61, the output of counter 78 a determinedthe timing of precision gate bias circuit 70 a to toggle current sinkMOSFET 71 a on and off. By controlling the timing of conduction ofcurrent I_(LED1) flowing in LED string 57 a including its duty factor D,i.e. its on time each Vsync period, the brightness of LED 57 a isprecisely controlled. The bit data loaded into Dot register 77 a issimultaneously interpreted by D/A converter 79 a to set the referencecurrent αI_(ref) feeding precision gate bias circuit 70 a. Thisreference current sets the analog magnitude of LED current I_(LED1)flowing in MOSFET 71 a and in LED string 57 a whenever the particularchannel is toggled on and conducting. It has no bearing of the MOSFET'scurrent when counter 78 a toggles the particular 69 a channel off. Thesame process occurs simultaneously for all n channels, i.e. from channeldrivers 69 a through 69 n.

The value of reference current αI_(ref) is set in any given channeldriver in two ways. Firstly the value of I_(ref) is set by a precisionresistor R_(set) present in each channel driver 69 a through 69 n. Aprecision trimmed voltage reference V_(ref) present within LED driver IC69 (but not shown) is converted into the precision reference currentI_(ref) by the value of the resistor R_(set) such thatI_(ref)=V_(ref)/R_(set). The resistor R_(set) may be integrated providedthat it is trimmed for absolute accuracy during manufacturing, or maycomprise a discrete precision resistor, one per channel, externallyconnected to each channel of LED driver IC 69. While the value ofR_(set) could conceivably be varied from channel-to-channel, it isgenerally preferable to use precisely the same value of R_(set) in everychannel to maximize the channel-to-channel matching and to vary thechannel reference current through the digitally controlled value of theparameter α, as determined by the digital value stored in the Dotregister of every channel.

For example in channel driver 69 a, the 8-bit word stored in Dotregister is converted into one of 256 levels for the multiplier α,allowing the current in MOSFET 71 a and in LED string 57 a to be setanywhere from 0% to 100% ·I_(ref) in 256 steps, i.e. in increments of0.39% per step whenever MOSFET 71 a is on and conducting. The sameoperation occurs in all channel drivers 69 a through 69 n, enablingdigital control of LED current in every LED string 57 a through 57 n viadigital bus 73.

It should be noted that in an LED backlit HDTV it is preferable tochange LED brightness using the digital PWM dimming method and counters78 a through 78 n than it is to use Dot registers 77 a through 77 nchanging the corresponding value of αI_(ref) in each channel, primarilybecause the color temperature of white LEDs is a function of current.Running the LED strings across the display at dramatically differentcurrents can adversely result in color aberrations in the display image.

To maintain the proper current in every LED string including the LEDstring with the highest forward drop, current sense feedback circuitsCSFB 72 a through 72 n have been included to determine in real timewhich string exhibits the highest voltage and to use that information asfeedback to SMPS 52 to set its output +V_(LED) to a voltage justslightly higher than the LED string with the highest forward voltage.

The CSFB circuits are connected in daisy chain fashion, i.e. in series“head to toe”, with the input 73 b into CSFB circuit 72 a coming fromthe output of CSFB circuit 72 b, the input 73 c into CSFB circuit 72 bcoming from the output of CSFB circuit 72 c (not shown), and so on. EachCSFB circuit passes the lower of its input voltage or the voltage on thedrain of the corresponding current sink MOSFET in the channel to itsoutput, until the last CSFB circuit 72 a has an output 73 a representingthe lowest drain voltage in the IC (and hence the highest forwardvoltage LED string) provided as the CSFB feedback signal to SMPS 52. Thefirst CSFB circuit in the string CSFB 72 n must have its input tied tothe highest convenient voltage, e.g. V_(logic) or V_(driver).

Since, however, all the LED strings in a LCD backlight for color HDTVsare white LEDs, probably from the same manufacturer and even the sameproduction batches, the variation in forward voltage of the LED stringsprimarily results from natural stochastic variability in the LEDs'manufacture, not from functional differences in the types of LEDs beingdriven.

SUMMARY OF BACKGROUND

In conclusion, prior attempts to adapt LED technology forphotobiomodulation and medically for phototherapy suffer from grosslyinadequate flaws in their mechanical and electrical design. The LEDdriver circuitry used to implement early attempts at phototherapyessentially comprise constant voltage drive LED torchlights unable tomaintain consistent LED operation under conditions of changing voltages,LED currents, or fault scenarios. Operating essentially as fixedfrequency lamp dimmer circuitry, they also lack the ability tofacilitate pattern sequencing and waveform synthesis—sequences andwaveforms potentially beneficial in maximizing photobiomodulation andthe therapeutic benefit therewith.

Similarly inadequate, the hardware of present day LED arrays suffer frommediocre mechanical design resulting in poor reliability from excessivewire interconnections in the LED array and an inability to maintain aconstant position or conform the shape of an LED array to a patient fora consistent optical penetration depth, especially during treatmentsnecessarily exceeding tens of minutes, or longer.

While constant current LED backlight driver ICs for HDTVs electricallyinclude better functionality for driving large arrays of LEDs than theaforementioned LED torchlight designs, their features are specificallyengineered to address issues in illuminating LCD displays includingsynchronization to video display timing signals and the ability to adaptin brightness in response to video content—functions completelyirrelevant to implementing a phototherapeutic device. Moreover, in theirpresent form, such HDTV backlight drivers do not enable or evenanticipate the need for generating complex waveforms, performingalgorithmic sequencing, synthesizing varying frequencies, or drivinginhomogeneous LEDs, ones of differing construction, wavelength andforward voltages.

What is needed is a new design for LED phototherapy implemented todeliver the highest degree of photobiomodulation uniformly andconsistently for extended durations, ideally with extensive programflexibility and features controllable by the attending physician.

BRIEF SUMMARY OF THE INVENTION

In the phototherapy process of this invention, defined patterns (e.g.,square-wave pulses) of electromagnetic radiation (EMR) having one ormore wavelengths, or spectral bands of wavelengths, are introduced intoa living organism (e.g., a human being). The radiation is normallywithin the infrared or visible parts of the EMR spectrum. EMR of asingle wavelength may be used, or the pattern may include EMR havingtwo, three or more wavelengths. Rather than consisting of radiation of asingle wavelength, the EMR may include spectral bands of radiation,often represented as a range of wavelengths centered on a centralwavelength, e.g., λ±Δλ. The pulses may be separated by gaps, duringwhich no radiation is generated, the trailing edge of one pulse maycoincide temporally with the leading edge of the following pulse, or thepulses may overlap such that radiation of two or more wavelengths (orspectral hands of wavelengths) may be generated simultaneously.

The EMR is preferably generated by light-emitting diodes (LEDs) that arearranged in serial “strings” connected to a common power supply. EachLED string may comprise LEDs designed to generate radiation of a singlewavelength or band of wavelengths. The LEDs may be embedded in aflexible pad that designed to fit snuggly against a skin surface of ahuman body, allowing the target tissue or organ to be exposed to auniform pattern of radiation.

Each of the LED strings is controlled by a channel driver, which in turnis controlled by a microcontroller. The microcontroller includes a“pattern library” of algorithms each of which defines a particularprocess sequence of pulses of the EMR generated by the LED strings.Using a display, keyboard or other input device, a doctor or cliniciancan select the particular algorithm (process sequence) that is suited tothe condition or disease being treated.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphical illustration of the electromagnetic spectrum ofradiation, contrasting phototherapy to radiation therapy.

FIG. 2 is a schematic circuit diagram of a voltage-based LED driver anddimmer circuit.

FIG. 3 is a graph illustrating the impact of battery discharge on LEDcurrent in voltage based LED drivers.

FIG. 4A is a view illustrating the problem of maintaining a consistentposition and phototherapy depth with a handheld LED wand or torchlight.

FIG. 4B is a detailed view illustrating the problem of maintaining aconsistent phototherapy depth over large area with a mechanicallyinflexible LED array.

FIG. 5A is a cross sectional view of a white LED backlight used in LEDHDTVs as seen by the human eye.

FIG. 5B is a schematic circuit diagram of constant-current LED driver ofthe type used as a HDTV backlight.

FIG. 6A is a series of graphs illustrating fixed frequency PWM backlightbrightness control in a 2D-mode LED backlit HDTV.

FIG. 6B is a series of graphs illustrating fixed frequency PWM backlightbrightness control in a 3D-mode LED backlit HDTV.

FIG. 7 is a schematic circuit diagram of an architecture for a LEDbacklit HDTV.

FIG. 8A is a schematic illustration of an LED pad illuminatingepithelial tissue.

FIG. 8B is a graphical depiction of the physical mechanisms ofphotobiomodulation.

FIG. 8C depicts photosynthesis (ATP generation) in animal cells.

FIG. 8D is a chart showing the hierarchical impact of animalphotobiomodulation in Homo Sapiens.

FIG. 9A is an energy band schematic representation of photoexcitation ofmolecules.

FIG. 9B is an energy band schematic representation of photobiomodulationfor various light wavelengths.

FIG. 9C is a schematic representation of narrow band photobiomodulation

FIG. 9D is an energy band schematic representation of bio-interferencein broadband photobiomodulation.

FIG. 9E is an energy band description of observed relative therapeuticefficacy as a function of spectral bandwidth.

FIG. 10A is a flow chart of an exemplary dynamic phototherapy protocolcomprising sequential operation of LED strings of differing wavelengths.

FIG. 10B is a timing diagram of the exemplary dynamic sequentialphototherapy protocol shown in FIG. 10A.

FIG. 10C is an illustration of the details of waveform representation.

FIG. 10D is a flow chart of an exemplary dynamic phototherapy protocolcombining sequential and parallel operation of LED strings of differingwavelengths.

FIG. 11 is a schematic diagram of a dynamic phototherapy system and userinterface for programmable waveform synthesis.

FIG. 12 is a schematic representation of a dynamic phototherapy systemwith programmable waveform synthesis capability.

FIG. 13 is a diagram of independent multichannel LED control in adynamic phototherapy system.

FIG. 14A is a diagram of an example of register data for controlling thecurrent in specific wavelength LED strings in a multi-wavelength dynamicphototherapy system.

FIG. 14B is a diagram of an example of register data for controlling thecurrent a different wavelength LED strings in a dynamic phototherapysystem.

FIG. 15A shows timing diagrams of waveforms at various synthesizedfrequencies in a dynamic phototherapy system.

FIG. 15B shows timing diagrams of multiple-wavelength LED strings atvarious synthesized frequencies in a dynamic phototherapy system.

FIG. 15C is a timing diagram of multiple-wavelength LED strings in adynamic phototherapy system at the system's maximum synthesizedfrequency.

FIG. 15D is a timing diagram of an alternative method of synthesizinghigh frequencies in dynamic phototherapy system using a variable clocksignal.

FIG. 15E is a timing diagram for synthesizing frequencies in a dynamicphototherapy system equal to a V_(sync) frequency.

FIG. 15F is a timing diagram for synthesizing frequencies in a dynamicphototherapy system lower than a V_(sync) frequency.

FIG. 16 is a timing diagram illustrating data register updates forconcurrently synthesizing two different photoexcitation frequencies.

FIG. 17A is a timing diagram for synthesizing fixed frequencies in amulti-wavelength dynamic phototherapy system with PWM brightness control

FIG. 17B is a timing diagram for synthesizing multiple frequencies inmulti-wavelength dynamic phototherapy system with PWM brightnesscontrol.

FIG. 17C is a timing diagram for synthesizing dynamically varyingfrequencies in multi-wavelength dynamic phototherapy system withconstant on-time brightness control

FIG. 18 is a timing diagram for parallel driven multi-wavelength LEDstrings with independent PWM brightness control (blending) in a dynamicphototherapy system with fixed frequency synthesis.

FIG. 19 is a graph of the current in an LED string as a function of thedata stored in an I_(LED) register in a dynamic phototherapy systemusing a programmable D/A converter.

FIG. 20 is a graph of optical output power at different wavelengths as afunction of data stored in an I_(LED) register, illustrating brightnesscompensation.

FIG. 21 is a circuit diagram illustrating the loading of I_(LED)register data for brightness compensation.

FIG. 22 is a graph of the turn-on current transient waveform,illustrating the benefit of phase delay.

FIG. 23A is a flow chart of an exemplary dynamic phototherapy protocolillustrating full parametric control of the duty factor D, the synthesisfrequency f_(synth), the phase delay φ, and the reference currentmultiplier α.

FIG. 23B is a timing diagram for synthesizing dynamically varyingfrequencies in multi-wavelength phototherapy system with dynamicbrightness control.

FIG. 24 is a block diagram representing the functions of themicrocontroller in a phototherapy system according to the invention.

FIG. 25 is a flow chart of the set up and operation of themicrocontroller in a phototherapy system of the invention.

FIG. 26 is a plan view and equivalent circuit of the LED pad.

FIG. 27 is a cross-sectional view of a flexible LED pad conforming to acurved surface.

FIG. 28 is a graph of radiant intensity (normalized power output) versuswavelength LEDs of various wavelengths.

FIG. 29A is a graph of the relative absorption coefficient of variousbiochemicals as a function of the wavelength of incident EMR.

FIG. 29B is a graph of the relative absorption coefficient of internaltissues as a function of the wavelength of incident EMR.

FIG. 30 is a graph of the relative absorption coefficient of surfacetissues as a function of the wavelength of incident EMR.

DESCRIPTION OF THE INVENTION

Principles of Photobiomodulation

Photobiomodulation involves the controlled delivery of photons intoliving cells and tissue stimulating a biochemical response. When appliedto medical science, the use of photobiomodulation to produce abeneficial or therapeutic result is herein referred to as“phototherapy”. A number of variables can affect photobiomodulation,including the organism, tissue, cell, or organelle being illuminated;the wavelength(s) of the light used, the absorption depth and scatteringproperties of the light at the impinging wavelength in the targeted andintervening tissue; the power, timing, duration, and frequency of thephotoexcitation, including the potential sequencing of multiplewavelengths, the specific biochemical reaction being affected, and intherapeutic cases the nature of the injury or condition requiringtreatment.

FIG. 8A schematically illustrates in cross section, the elements of aphototherapy delivery system, including a flexible circuit board 81, anLED array 93 a through 93 e, a flexible, biologically inert encapsulant82, a flexible aseptic hygienic barrier 85, and an LED driver IC 86. TheLED array 93 a through 93 e and its enclosure, collectively herein as anLED “pad”, ideally should be sufficiently flexible and bendable to fitsnugly against a patient without damaging the interconnecting conductorsor electronic components within the pad. Light 83 then illuminatesepithelial and epidermal tissue layers 36 and 37 accordingly, as shownby illumination and absorption profile 84. In the LED pad as shown,encapsulant 82 may cover the lenses of LEDs 93 a through 93 e providedit is sufficiently thin and transparent at the LED wavelength not toblock the LEDs' light output.

Note: As used herein, the terms “LED driver IC” and “LED driver” areused interchangeably to refer to an IC that contains circuitry forcontrolling multiple channels, each channel being represented by an LEDstring. The term “channel driver” is used to refer to the circuit withinan LED driver IC that is used to control a single LED string (channel).

Photobiomodulation starts with photoexcitation of atoms and molecules,represented pictorially in FIG. 8B where an impinging photon 90 having awavelength λ and a corresponding EMR frequency ν (denoted by the Greekletter ν, or “nu”) strikes a molecule 91, breaking chemical bonds 92 andmaking new bonds, and potentially ejecting charges 93. The absorbedenergy 90 may be divided into any combination of changes in the kineticenergy (KE) and potential energy (PE) in the system including structuraltransformations of molecules into higher or lower energetic states 94,charge transport 95 either by drift conduction qE in a local electricfield or diffusion conduction dNq/dx due to concentration gradients,and/or by thermal vibrations 96 of molecules from heating or in quantumdynamical terms by phonons. These photon-induced or “photo-excited”reactions can happen involving any number of molecules within the cell.

Some of the reactions may involve purely inorganic components whileothers involve organic molecules, or both. As represented in FIG. 8C, atleast one confirmed photobiological process 96, the impinging photons 90are absorbed by cytochrome-c oxidase (CCO) 100 which functions withinmitochondria 97 as a battery charger, pumping adenosine monophosphate(AMP) into a higher energy state adenosine diphosphate (ADP), andultimately pumping ADP to the highest energy state molecule adenosinediphosphate or ATP 101. For its ability to store energy, CCO 100 issometimes referred to as a proton pump. Alternatively, if we considerATP 101 as a battery at a cellular level, then CCO 100 could beconsidered the battery charger. Conversely, when ATP 101 breaks downinto ADP or AMP it releases significant energy 102, over 6 k-calorie permole.

As an organelle in an animal cell 98, mitochondria 97 provides energy ina symbiotic relationship, where cell 98 provides a beneficiallyprotective environment for mitochondria 97. Using CCO 100, mitochondria97 can convert sugars, the byproduct of digestion, into energy orthrough photobiological process 96, it can absorb light to generate ATP101.

The energy generation resulting from photobiomodulation of mitochondriaresults in a cascade of biochemical, electrical and thermal effectsaffecting an organism at every level, from the organelle and cell, totissue, organs and the entire organism (including homo sapiens).Reported effects are tabulated in FIG. 8D including exemplaryillustrations 103 of the affected cell, tissue, organ or systems alongwith specific descriptions of observed photobiological responses 104. Inparticular note that the activation of ATP leads to enzymatic activity,the creation of intercellular catalysts and the onset and accelerationof DNA transcription, RNA translation and protein synthesis, i.e.photosynthesis in animals. One byproduct, nitric oxide (NO), is found tobe key in promoting tissue repair and granulation, forming newcapillaries and dilating arteries to increase blood flow and cellularoxygenation, while repairing nerves, blocking pain, and modulatingimmune response to suppress infection and inflammation. While thesemechanisms are beyond the full scope of this disclosure, the referencedarticles may provide added insight into these biochemical andcytological mechanisms.

Another important consideration in photobiomodulation is that ofphotoexcitation frequency. Not to be confused with the wavelength of thelight λ and its corresponding electromagnetic frequency ν_(EM), thephotoexcitation frequency f_(synth) describes the repeated periodwhereby a bio-organism exposed to EMR shows the ability to cyclicallyabsorb greater amounts of energy than at other frequencies. In physics,these resonant frequencies are a naturally occurring property of matterabsorbing and releasing energy in periodic fashion. Such resonantfrequencies are typically orders of magnitude orders of magnitude slowerthan the oscillating frequency of the infrared and visible light itself,corresponding to atomic level transitions—transitions occurring atfrequencies and having corresponding energy levels similar to thewavelengths of light that an atom absorbs or emits.

Since biochemical molecules, organelles, cells, tissues, organs andorganisms all have mass and are held together by chemical and mechanicalforces, then all these forms of biological matter must necessarilyexhibit vibrational movement and resonance, each with its owncharacteristic frequency. Primarily because of the masses involved,organs and tissues resonate at much lower frequencies than the vibrationof molecules and of atoms within a molecule.

In animals, the operation of numerous organs such as the heart, muscles,the nervous system and the brain also operate involving electrical orelectrochemical processes. These electrical signals also operate atcertain specific frequencies and also can exhibit resonance, primarilyinvolving electro-chemical oscillations rather than thermal vibrations.In the 1960s Nogier et al. first discussed the influence of periodelectrical signals stimulating human tissue with micro-currents. Laterthe USSR was also to conduct experiments using ceramic lamps to inducephotoexcitation at controlled frequencies, but the work remained largelyunpublished.

While the dynamics are still poorly understood, clearly any deviceintended to stimulate photobiomodulation should be capable ofcontrolling not only the brightness and wavelength of light, but alsothe frequency of any periodically repeating pattern of photoexcitation.

Impact of Spectral Bandwidth on Photobiomodulation

Herein, the electronic control of photons for the purpose ofphotobiomodulation is referred to as “biophotonics”. To design andconstruct a biophotonic apparatus to perform phototherapy with maximumefficacy, it is important to examine the physical mechanisms ofphotoexcitation consistent with the limited empirical evidence existingtoday.

The band theory of solids normally used to model the behavior of solidstate electronics and semiconductor devices, once adapted for moleculesand molecular bonds, can provide additional insight to the mechanismsoccurring during photoexcitation of living cells, organelles, and themolecules contained within. A similar method was employed insightfullyby Linus Pauling in his landmark book “The Nature of the Chemical Bond,”[Cornell University Press, Ithaca, N.Y., 1939, 3^(rd)edition 1960] andis still used today in biochemistry and in the study and development oforganic semiconductors. While the topics discussed in this disclosureare not specifically related to the molecules considered in the citedtextbook, a similar methodology of analysis using energy bands andelectron orbitals is insightful in explaining observed results and inoptimizing phototherapeutic strategies.

FIG. 9A illustrates three possible interactions of EMR with matter. Inthe graphics, the rectangular lines or energy bands 109 representvarious potential energy states of a molecule in various forms with E₀being the ground or lowest energy state, E₁ at a higher energy state, E₃at even a higher energy, and so on. In an individual atom, these bandsrepresent discrete energy levels and the dot represents charge presentat that energy level similar to that proposed by Niels Bohr in at thebeginning of the 20^(th) century (the so-called Bohr atom). The bandtheory was later adapted to groups of interacting atoms in a crystal,replacing discrete energy level with bands of allowed energy statesseparated by energy gaps E_(g) where no stable quantum energy level ispresent. When matter absorbs light of sufficient energy to overcomethese energy band gaps, charges experience a corresponding energytransition from a ground state to an elevated energy state or band.

For example in the leftmost graphic, when a photon hits the materialrepresented by bands 109, a charge at the ground state E₀ jumps 111 toan excited state E₃. To manifest this transition, the impinging photonmust carry energy greater than the bandgap or the quantum transition 111will not occur. The energy E carried by the photon, as described by A.Einstein, is proportional to its frequency, as given by the well knownrelation E=hν=hc/λ with ν=ν_(EM) being the frequency of the EMR, λ itswavelength, h being Planck's constant, and c being the speed of light.Provided that the photon energy E exceeds the minimum energy needed toeffect a change in the potential energy of the molecule, shownmathematically as E>Eg, then transition 111 will occur. After the chargejumps up to the E₃ state, it falls back to a lower energy state E₁.Since this smaller transition does not involve significant energy, aphonon 114 (a quantum of vibrational energy) is released, contributingto molecular vibration and heating.

If instead of interpreting this diagram as energy bands in a crystal, wenow consider the energy bands as representing energetic states of one ormore interacting molecules, the process of energy absorption and energyre-release can be understood in a similar, albeit metaphoric, manner.Referring again to FIG. 9A, the left graphic involving a lower energyphoton excites the molecule into state 112, one of the lower allowedenergetic states and results in phonon 114. The middle graphicrepresents a case where the impinging photon 120 has a higher energythan photon 110, and results in photoexciting the molecule 121 to stateE_(S) only to collapse back to stable state 122 and release a phonon 124in the process.

In the rightmost graphic, an even higher energy photon 130, having ahigher frequency ν_(EM) and shorter wavelength λ than photon 110 orphoton 120, imparts so much an energy 131 that it breaks the moleculeapart releasing a free charge 135, which is able to conduct freelywithin a cell or to engage in intercellular charge transport.

FIG. 9B expands the described phenomenological energy band analysis to acollection of molecules and their interaction with photons having not asingle wavelength but representing a spectral band of frequencies andwavelengths. In the graph, the vertical axis represents the chemicalpotential energy (PE) of the molecules represented by energy bands 109,which have a variety of energetic states E₀ to E₁₂. The horizontal axisdescribes the relative frequency (and wavelength) of impinging photons,with the left side of the graph representing lower EMR frequenciesν_(EM) (and hence increasing EMR wavelengths λ) and the right siderepresenting higher EMR frequencies ν_(EM) (decreasing EMR wavelengthsλ). The transitions represent the many and varied interactions ofmolecules with different wavelength photons.

As shown, photons emitted from an array of light emitting diodes LED1 donot comprise a single wavelength but a spectral band of frequencies andwavelengths 140 having a nominal value λ₁ and varying above and below bysome amount ±Δλ₁, i.e. comprising a spectral band λ₁±Δλ₁. SinceE=hν_(EM)=hc/λ, then spectral band 140 not only represents a range infrequencies and wavelengths but in corresponding photon energies.Similarly, the light emitted from arrays of light emitting diodes LED2and LED3 do not comprise single wavelengths, but spectral band 150 withwavelengths λ₂±Δλ₂ and spectral band 160 with wavelengths λ₃±Δλ₃respectively, where λ₁>λ₂>λ₃. For example, an array of light emittingdiodes LED1 may constitute a center wavelength λ₁=875 nm and a spectralbandwidth varying from 860 nm to 890 nm, so that λ₁±Δλ₁=875 nm±15 nm inthe infrared band. Similarly an array of light emitting diodes LED2 maycomprise a spectrum λ₂±Δλ₂=740 nm±15 nm in the near infrared band, andLED3 may comprise λ₃±Δλ₃=670 nm±15 nm in the long wavelength portion ofthe visible red spectrum.

The spread Δλ in the spectrum of an array of LEDs results from twostochastic, i.e. random, physical mechanisms. First, in the manufactureof LEDs, the consistency of the bandgap for bandgap engineered materialsand the presence of defects, dislocations and unintended impuritiesaffects the light wavelengths emanated from each individual LED. Second,the center values of all the LEDs in the array collectively exhibit astatistical distribution even if each LED only emitted a singlewavelength of light. Since these two random effects have physicallyindependent origins, then the statistical standard deviation σ_(λ) addsin quadrature, i.e. where σ_(λ)=SQRT [σ₁ ²+σ₂ ²] and where σ₁ and σ₂represent the standard deviation within an individual LED and in acollection of LEDs. The total spectral width ±Δλ of an array of LEDs canbe statistically approximated by the three-sigma distribution, so that±Δλ=±3σ_(λ).

Photoexciting the molecules having energy bands 109 exclusively withwavelengths 140 from an array of light emitting diodes LED1 results in acollection of energy transitions 165 b including exemplary transitions113, 114, and 115. Note that not every energy state is stable. Forexample, energy state E₁ may under certain ambient conditions oftemperature, humidity, pH, etc. be unstable. Exciting the molecule intothat state immediately or after some duration of time results in themolecule collapsing back (arrow 115) to its ground state E₀. Twoimportant observations can be made from this analysis: first, that thespectral band emanating from an array of LEDs invokes not one, but anumber of molecular reactions and energy transitions; and second, thatwith its long wavelengths, array of light emitting diodes LED1 isincapable of photoexciting molecules to any potential energies above E₄.

In a similar manner, an array of light emitting diodes LED2 havingshorter wavelengths 150 photoexcites a number of reactions includingthose represented by arrows 123, 124, 122, 125, 126 and 127. Thesereactions and state changes, while overlapping some energy transitions165 b, tend to involve higher energy levels than reactions photoexcitedfrom an array comprising longer wavelength LED1 light emitting diodes.For example, an array of light emitting diodes LED2 invokes transitionsup to energy level E₇ whereas an array of light emitting diodes LED1results in transitions that never exceed energy level E₄. Some levels,such as E₅ may in fact be unstable where transitions to such statescollapse back to the ground state E₀ for the affected molecule.

An array of light emitting diodes LED3 having the shortest wavelengths160 and therefore the highest photon energies, invokes the highestenergy transitions 161, 162, 163 up to energy level E₁₀, well beyond thereactions and energy transitions induced by photoexcitation from arraysof light emitting diodes LED2 or LED1. The highest energy statephotoexcited from an array of light emitting diodes LED3, specificallyE₁₀, is below energy levels E₁₁ or E₁₂ triggering hostile or severemolecular instability.

FIG. 9C illustrates the impact of very narrow bandwidth photoexcitation165. In this case the impinging EMR has a very bandwidth λ₃±δλ₃ whereδλ₃ is roughly an order of magnitude narrower than Δλ₃, i.e. whereδλ₃<<Δλ₃. For example, instead of λ₃±Δλ₃=670 nm±15 nm, an example of anarrow bandwidth illumination is λ₃±δλ₃=670 nm±1.5 nm. Such narrowbandwidth is typically emanated from lasers and not from LEDs. Eventhough the center wavelength is the same value λ₃ as an array of lightemitting diodes LED3, the resulting reactions and transitions 165 ausing a narrow bandwidth laser are dramatically fewer than the reactionsand transitions resulting from using array of light emitting diodesLED3. Too few reactions, shown here only to comprise transitions 166 and167, can negatively impact the magnitude of photobiomodulation,reactions that rely on a plethora of catalytic and biochemicalinteractions. In phototherapy, treatments involving narrow bandwidth EMRinvoke minimal photobiomodulation suffering reduced therapeutic benefitcompared to that of broader spectrum LEDs.

Although narrow spectrum photoexcitation exhibits lower efficacies instimulating cell repair than broader spectra, such protocols holdpromise in targeting and destroying specific unwanted cells, organisms,or pathogens infecting a host. Selective targeting for cellulardestruction rather than cell and tissue repair is a subject beyond thescope of this disclosure.

While overly narrow bandwidth photoexcitation may be ineffective instimulating therapeutic benefits, overly broad bandwidth photoexcitationmay also be ineffective and even detrimental. FIG. 9D illustrates onemechanism by which simultaneous photoexcitation by arrays having twobandwidths of light emitting diodes may produce undesirable results. Asdescribed previously, a collection of molecules with energy hands 109photoexcited by an array of light emitting diodes LED2 with a spectralband 150 and wavelengths λ₂±Δλ₂ stimulates a variety of transitions 123,124, 125, 126, 127 and others, herein collectively described as“beneficial” or therapeutic transitions. If however simultaneous to thearray of light emitting diodes LED2 being illuminated, the samemolecules are photoexcited by array of light emitting diodes LED3 havingits spectral band 160 and wavelengths λ₃±Δλ₃ the result may includetransitions not present when light emitting diodes arrays LED2 or LED3are used independently and not concurrently.

These unexpected and undesirable transitions 165 c occurring from theconcurrent illumination and photoexcitation from both LED2 and LED3arrays of light emitting diodes include stimulating transitions tounstable and even hostile states as exemplified by transition 139. Theformation of hostile energy states E₁₁ and E₁₂, in turn may depending onambient conditions lead to the impairment or destruction ofbiochemically beneficial molecules. Mechanisms leading to undesirabletransitions 165 c include optical wave interference producing spatiallydependent crests and valleys in the energy distribution in cells andtissue, two step transitions where spectral band 150 photoexcites amolecule to energy band E₄ or E₆ and spectral hand 160 furtherphotoexcites the molecules to hostile energy hands E₁₁ and E₁₂,catalytic effects making energetically unfavorable reactions morelikely, etc.

The term “hostile” state is not meant to imply the resulting molecule istoxic, mutagenic or carcinogenic to the cell, but that the transitioncounters the formation or activation of beneficial molecules that wouldotherwise be formed by photobiomodulation stimulated from thephototherapy treatment. The result is primarily a reduction in benefitfrom the photoexcitation manifested therapeutically as diminishedefficacy. This diminished efficacy is herein referred to as molecular“bio-interference”. Mechanistically, bio-interference from undesirabletransitions 165 c represents the breaking apart or biochemicaldeactivation of beneficial molecules, the impairment of the formation ofbeneficial molecules, the formation of catalysts that impair theformation or activity of beneficial molecules, the formation ofmolecules that change the surrounding pH adversely affecting chemicalreactivity of beneficial molecules, and any mechanism divertingimpinging energy otherwise involved in the formation of beneficialmolecules.

One possible scenario where the concurrent application of arrays ofdiffering wavelength LEDs will likely avoid significant bio-interferenceis in spectral “blending”. In spectral blending, arrays of lightemitting diodes comprising two LED types and having different spectralbands are concurrently illuminated but where one LED array is dimmed toa power level (brightness) that is small fraction of the other. Forexample if an array of LEDs comprising LED2 having a spectral bandλ₂±Δλ₂ is powered at full brightness (at a duty factor D₂=100%) and asecond array of LEDs comprising LED3 having a spectral band λ₃±Δλ₃ ispowered to a brightness one tenth that of the LED2 array (i.e. whereduty factor D₃=10%), the statistical likelihood of significantbio-interference is minimal because only a small fraction of photons areeven capable of invoking undesirable transitions. No evidence existstoday that blending offers any photobiomodulation benefit, butconceivably a low population of “hostile” catalysts may in limitedconcentrations offer benefits in suppressing the formation of other evenmore hostile molecules. An analogous example in nature is that organismsexposed to normal ambient levels of ionizing radiation are often morerobust than those completely insulated from all ionizing radiation, inpart because the radiation suppresses foreign invaders and kills weakercells so a stronger cell population can flourish.

Considering all the aforementioned mechanisms, the behavior andimportance of spectral bandwidth on photobiomodulation and its impact onthe therapeutic efficacy of photoexcitation is summarized in FIG. 9Ecomprising a graph with an abscissa measuring the relative spectralbandwidth (λ_(max)−λ_(min)) and the ordinate representing the relativetherapeutic efficacy, i.e. a measure of the degree of beneficialphotobiomodulation. The graph is predicated on the assumption that theimpinging frequencies can be absorbed by the targeted cells and the EMRis not blocked or absorbed by any intervening tissue present between thetargeted cells and the light source.

That caveat aside, region B illustrates illumination of tissue usingrelatively broad spectral bandwidth EMR, e.g. in the range of tens ofnanometers, where photoexcitation results in diverse biochemicalreactions and high therapeutic efficacy 161 b. Such a condition may beachieved independently using arrays of light emitting diodes LED1, LED2or LED3 with corresponding spectral bands 140, 150 or 160, respectively,by not concurrently in combination. Region C representing illuminationfrom broad spectral bandwidth EMR, e.g. an order of magnitude broaderthan region B, exhibits a diminished therapeutic efficacy 161 c due tobio-interference resulting from overly broad spectra photoexcitation.Such a condition can arise from concurrent illumination from arrays ofLED2 and LED3, i.e. the simultaneous presence of spectral bands 150 and160, or from wide spectrum light from heat lamps, sun lamps, andunfiltered sunlight.

Region A illustrates illumination of tissue using very narrow spectralbandwidth EMR, e.g. in the range of a few nanometers or less, producesfew and highly specific biochemical reactions too limited to invokesubstantial photobiomodulation or significant therapeutic results. Sucha condition is typical to illumination by laser light—EMR by its verynature tuned to a narrow bandwidth. Because of the highly specificreactions, it relative therapeutic efficacy 161 a in stimulatingcellular repair is therefore diminished but may still be better thanusing overly broad spectral bandwidth light. Pragmatically speaking,laser light also suffers from a small spot size compared to the areailluminated by LEDs. That said, narrow bandwidth photoexcitation, albeitat higher power levels, may be used to invoke targeted destruction ofcells, organelles or biochemical molecules.

While the phenomenological description of the impact of spectralbandwidth on photobiomodulation described herein is extrapolated fromthe band theory of solids, the resulting curve of therapeutic efficacyversus spectral bandwidth is consistent with our own empirical data,measurement, and observation. The result is also consistent with theearly studies performed by NASA where sunlight and broad spectrum lightfrom incandescent lamps were found to be less efficient at stimulatinghealing than narrow spectrum light from infrared lasers.

While phototherapy efficacy today is measured by visual inspection oftreated tissue and by patient interviews, in the future, at least in theinfrared spectrum, it may be possible to image, i.e. “see”, molecularinteractions in real time during photobiomodulation, conceivably usingthe same infrared light being used for photoexciting the tissue orcells.

The conclusion of this section is that, in general, LEDs exhibit aspectrum of wavelengths better suited for photobiomodulation and forphototherapy than lasers, but that various spectrum LEDs, if desired,should be used sequentially rather than concurrently to avoidbio-interference adversely limiting phototherapy efficacy. Common sensealso dictates that photobiomodulation of any specific organ, tissue,cell or organelle requires that any intervening tissue (e.g. blood,water, fat) does not block or absorb significant portions of thewavelength of EMR being applied, and that a combination of variouswavelengths are needed for photoexcitation of different organs andtissues.

An apparatus properly designed for maximizing the efficacy of medicalphototherapy must therefore deliver a plurality of light wavelengths ina variety of sequences using an array of light sources covering arelatively large area. Ideally these sequences and LED settings shouldbe adjustable and programmable to facilitate the maximum in userflexibility, especially important in capturing and perpetuating thelearning of clinicians and attending physicians. While the primaryfunction should comprise a sequential application of differingwavelength LEDs, the apparatus should still be adaptable to includeconcurrent LED illumination (blending) and even laser treatments, shouldspecific beneficial therapies later be discovered.

Dynamic LED Driver Operation

A medical phototherapy apparatus should comprise a number of elementsincluding a flexible aseptic pad containing multiple strings ofindividually controlled LEDs having differing wavelengths, a controllerand LED driver circuit with to flexible interface capable ofprogrammable waveform synthesis and adjustable sequencing, a dynamicpower supply, and optionally a battery power source. The variablesrequiring electronic control in a medical phototherapy apparatus include

-   -   Independent control of the current in each string of LEDs    -   Independent control of the brightness of each string of LEDs        using PWM dimming    -   Independent control of the switching frequency of each LED        string    -   Independent control of the phased turn-on of LED strings    -   A dynamically adjusted voltage regulator maintaining requisite        LED currents with minimal power loss    -   Flexible sequencing of LED strings    -   Detection of LED faults with a choice of response options

Independent control of LED strings may be accomplished using dedicatedhardware and custom integrated circuits or by using a bus-controlleddriver IC interfaced to a programmable microcontroller. The advantage ofthe latter choice is that a microcontroller offers user flexibility inimplementing specific LED control algorithms while bus-controlled LEDdriver ICs, originally developed, for HDTV backlighting (as describedearlier in this disclosure) are now commercially available at reasonableprices. Regardless of the hardware platform, the LED drive system formedical phototherapy must support algorithmic control of waveformsynthesis in order to offer physicians their choice in therapeuticstrategies and protocols.

FIG. 10A illustrates one example of a sequential waveform synthesisalgorithm for phototherapy. As shown, in algorithm 170 only onewavelength LED array is illuminated at a time consistent with the priordiscussion for maximizing photobiomodulation and phototherapy efficacy.In this example, a number of operating conditions are preset to fixedconditions including the LED brightness set by duty factor D (Controlledby t_(on) and T_(sync)), LED sequencing to minimize power supply turn-onand inrush currents set by phase delay φ, the sync and system clockfrequencies set by T_(sync) and f_(θ) respectively, and the LED currentαI_(ref) set by I_(LED). The digital representation of the variablest_(on), φ, and I_(LED) are stored in digital registers for each channeland dynamically programmable through a digital bus interface bus.

In the FIG. 10A example, the sequence starts with photoexcitation 171 awhere an LED array with spectral band 150 comprising wavelengths λ₂±Δλ₂is illuminated for duration Δt_(a) followed by photoexcitation 171 bwhere an LED array with spectral band 160 comprising wavelengths λ₃±Δλ₃is illuminated for duration Δt_(h). In photoexcitation 171 c the LEDarray with spectral band 150 comprising wavelengths λ₂±Δλ₂ is once againilluminated, this time for a duration Δt_(c). After a timed delay 171 dof duration Δt_(d), an LED array with spectral band 140 comprisingwavelengths λ₁±Δλ₁ is illuminated 171 e for duration Δt_(c) as a finalstep in the sequential waveform synthesis algorithm 170.

As indicated by arrow 174, after the entire sequence is complete, it maybe repeated any number of times as programmed. During the firstsequence, or during every repetition, or during only some repetitionsphotoexcitation 171 c may be bypassed, i.e. skipped (arrow 173).Alternatively during some, all, or none of the cycles, laserphotoexcitation 171 f with spectral narrow spectral band 165 comprisingwavelengths λ₃±δλ₃ is illuminated for duration Δt_(f) betweenphotoexcitations 171 b and 171 c. Even with the same center wavelengthλ₃, the narrow spectral band 165 (e.g. emanating from an array oflasers) represents a tighter spectral distribution than spectral band160 produced by an array of LEDs, i.e. mathematically as δλ₃<<Δλ₃. Inwaveform synthesis algorithm 170, any duration Δt_(a), Δt_(b), Δt_(c),Δt_(d), Δt_(e), or Δt_(f) may dynamically be adjusted to any value,including zero.

FIG. 10B illustrates the output resulting from the main sequence ofwaveform synthesis algorithm 170 and the various elements used in itsconstruction. Waveform synthesis, in this case square wave pulses, isperformed using separate programmable counters for LED stringscomprising the various wavelength LEDs, namely λ₁, λ₂, and λ₃ with eachdistinct digital counter counting clock pulses from Clock θ. Timingdiagram 180 for Clock θ illustrates a continuous string of digital clockpulses each of period T_(θ). While the example illustrates the timeintervals Δt lasting on a few clock pulses for simplicity's sake, inpractice the Δt intervals likely last from minutes to tens of minutesand may include a repeated pattern of waveforms synthesized withprogrammed controlled synthesized frequencies f_(synth). The procedurefor waveform synthesis is described later in this disclosure.

Clock θ may be used to generate a second slower clock known as the Syncsignal (not shown) or alternatively both Clock θ and the Sync pulse maybe generated from a common digital oscillator and associated timers. Inan alternative embodiment, the Clock θ and the Sync pulse may begenerated from different oscillators operating at different frequencies,but synchronized using phased-lock-loop (PLL) circuitry, a method wellknown to those skilled in the art of digital clocked logic.

The counter used for toggling LED strings having wavelength λ₁ on andoff as shown in timing diagram 181, counts a series of pulses (e.g. 9pulses as shown) lasting for a duration Δt_(a) keeping the λ₁ LEDstrings off while the λ₂ LED strings are being illuminated. Immediatelythereafter the λ₂ LED strings are turned off and λ₁ LED strings areturned on causing the LED pad to emit λ₁ EMR illustrated by sine wave184 b for a duration Δt_(b) (e.g. 4 pulses as shown). The λ₁ LEDchannels stay off for the remaining duration (Δt_(c)+Δt_(d)+Δt_(e))shown.

For the purpose of clarification, timing diagram 181 (along with timingdiagrams 182 and 183), actually depict the superposition of threeseparate curves. Expanding diagram 181 into its three components in FIG.10C, waveform 185 depicts a digital “enable” signal having an off-stateshown as a digital “0” or a constant voltage of 0V, and an on-statedepicted by a digital “1” or a high-logic signal having voltageV_(driver). Illustrated alone, the digital waveform appears as one ormore square wave pulses. The same shape waveform 186 also represents thecurrent conduction waveform in any conducting strings of LEDs, having avalue of 0mA when the LED string is off and a current αI_(ref) when astring of LEDs is on and conducting. EMR output 184 illustrating a sinewave when the LED is on, conducting and illuminated depicts the EMRemanated from an LED of particular wavelength λ illuminated, and a flatline showing no EMR emission when its off

For convenience (and for brevity's sake), the three curves aresuperimposed in the waveforms shown in FIG. 10B and throughout thisdisclosure. It should be clarified that in the superimposed waveformrepresentation 181, EMR output 184 represents optical power, not anelectrical signal, while component waveforms for channel enable 185 andI_(LED) current 186 are purely electrical signals. No sine wave (otherthan unintended noise) exists in these electrical waveforms.

Furthermore, there is no ambiguity between the optical and electricalsignals because of their frequency ranges. An LED's EMR output has anelectromagnetic frequency ν_(EM) in the range of hundreds of megahertzto hundreds of terahertz while the frequency f_(synth) of thesynthesized excitation patterns are typically in the audio spectrum,i.e. below 20 kHz, and theoretically cannot exceed the frequency ofclock θ, which is at most in the megahertz range, five to eight ordersof magnitude lower frequency than EMR 184. For completeness, it shouldbe clear in these and subsequent waveform timing diagrams that the timescale for sine wave 184 is not the same scale as that of the much lowerfrequency digital waveforms.

Returning to the timing diagrams of FIG. 10B, the counter used fortoggling LED strings of wavelength λ₂±Δλ₂ on and off as shown in timingdiagram 182, turns on after one pulse illuminating λ₂±Δλ₂ LED stringsand the pad. These strings remain on for duration Δt_(a) while theΔ₂±Δλ₂ channel counter counts a series of 9 clock pulses after which theλ₂±Δλ₂ LED strings are turned off resulting in EMR illustrated by sinewave 184 a. Synchronous to λ₂±Δλ₂ LED strings being turned off, λ₃±Δλ₃LED strings are turned-on and illuminated After a duration of Δt_(b)comprising 4 clock pulses, the λ₃±Δλ₃ LED strings are turned off and theλ₂±Δλ₂ LED strings are turned on, causing the LED pad to again emitλ₂+Δλ₂ EMR as illustrated by sine wave 184 c for a duration Δt_(c) (e.g.for 3 clock pulses). Thereafter, the λ₂±Δλ₂ LED channels are turned offand remain off for the remaining duration (Δt_(d)+Δt_(e)) shown.

Meanwhile, the counter used for toggling LED strings of wavelengthλ₁±Δλ₁ on and off as shown in timing diagram 183 remains off forduration (Δt_(a)+Δt_(b)+Δt_(c)+Δt_(d)) or 22 clock pulses. Thereafter,the λ₁±Δλ₁ LED strings are turned on and the LED pad to emits λ₁±Δλ₁ EMR184 e for a duration Δt_(e) or 4 clock pulses, after which the λ₁±Δλ₁LED strings are also turned off. Because no LED string was active duringthe duration Δt_(d), i.e. over the interval between the 16 and 22 clockpulses, interval Δt_(d) appears as a 6-pulse delay.

The timing diagrams shown illustrate a clocked logic counter basedimplementation of sequential waveform synthesis algorithm 170 from FIG.10A, resulting in optical output 184 comprising the sequentialillumination of the LED pad by λ₂±Δλ₂ LED strings for a duration Δt_(a),λ₃±Δλ₃ LED strings for a duration Δt_(b), by Δ₂±Δλ₂ LED strings againfor a duration Δt_(c), a delay of duration Δt_(d) wherein no LEDs areilluminated, and finally by Δ₁±Δλ₁ LED strings for a duration Δt_(e).

As aforementioned, the importance of sequential operation should notpreclude the possibility of mixing more than one wavelength LEDconcurrently. As a modification of sequential waveform synthesisalgorithm 170, an example of sequential-parallel waveform synthesisalgorithm 177 shown in FIG. 10D, starts with single wavelengthphotoexcitation 171 a for duration Δt_(a) comprising spectra 150 ofwavelengths Δ₂±Δλ₂. This step is followed by the concurrent illuminationof two wavelength LEDs comprising photoexcitation 171 b for durationΔt_(b) comprising spectra 160 of wavelengths λ₃±Δλ₃ and simultaneouslyphotoexcitation 171 g for duration Δt_(g) comprising spectra 140 ofwavelengths λ₁±Δλ₁. For the purposes of this invention disclosure, thesimultaneous application of more than one wavelength of light isreferred to herein as “blending”. The brightness of each LED may beequal or dissimilar with one being brighter than the other, allowing arange of blends to be manifested. The duration of photoexcitation 171 band 171 g need not be the same. i.e. so that Δt_(b)≠Δt_(g). In suchcases, in algorithm 177 photoexcitation 171 c does not commence untilthe longer of the two durations, either Δt_(b) or Δt_(g), is completed.Algorithm 177 is then completed with single wavelength photoexcitation171 c for duration Δt_(c) comprising spectra 150 of wavelengths λ₂±Δλ₂.As indicated by arrow 174, the sequence can then be repeated for as longas desired

Waveform synthesis algorithms 170 and 177 are not meant to represent anexhaustive description of all the sequential and sequential-parallelsequences possible in phototherapy using multiple wavelength LEDs andlasers, but simply to illustrate by example a number of possiblesequences and the operational elements in these sequences. In theexamples, LED spectra 140, 150 and 160 are illustrated to havemonotonically decreasing wavelengths (and correspondingly increasingfrequencies) whereby λ₁>λ₂>λ₃, but the algorithm is not meant to implythat other combinations should be excluded, e.g. where λ₂>λ₁>λ₃. Alsolaser spectra 165 in algorithm 170 was shown to exhibit a center valuewavelength λ₃ the same as LED spectra 160, but other wavelengths such asλ₁ or even a completely different wavelength λ_(x) may be used insteadwithout altering the meaning or intent of the invention.

Aside from the algorithms needed to realize sequential multi-wavelengthphototherapy protocols, a hardware platform, or phototherapy apparatus,is needed facilitating the LED control and waveform generation, the LEDarray and pad, and a regulated voltage supply to power the LEDs andtheir drivers. An apparatus able to implement such LED control forphotobiomodulation and medical phototherapy is represented in FIG. 11,where LED drive and control apparatus 206 combining a multi-channel LEDdriver 207 with programmable microcontroller 209, dynamic switching-modepower supply (SMPS) 208, graphics interface 211 and keyboard 212, drivesan array comprising LED strings 205 a through 205 n embedded withinaseptic LED pad 204 illuminating tissue 202 of patient 201 with EMR 203(in this example red and near infrared light) and where a doctor orclinician 199 optionally manages the therapy session while monitoringthe patient's condition, before, after, and if desired, during thetreatment, on a display 198. Each of LED strings 205 a through 205 ncontains a group of serially-connected LEDs. In one embodiment each ofLED strings 205 a through 205 n contains an equal number “m” LEDs.

Central to LED drive-and-control apparatus 206, microcontroller 209contains a variety of LED settings and therapeutic algorithms, referredto herein as “pattern library” 210 a, stored inside its embeddednon-volatile memory. In practice, the programming and LED settings maybe permanently stored in a mask ROM, EPROM, in E²PROM or alternativelymay be downloaded from a hard disk drive (HDD) and temporarily stored inan SRAM or DRAM. Programming and/or LED settings may also be loaded viaUSB, Firewire, or Thunderbolt or any other proprietary connectors, overthe Internet via Ethernet, or wirelessly via WiFi, Bluetooth, 3G,4G/LTE, or other wireless protocols.

Microcontroller 209 interfaces to channel drivers 207 a through 207 nthrough a digital bus 213, e.g. using a serial peripheral interface(SPI) protocol, implemented in its digital bus port 210 b. Within eachof its “n” channels, LED driver IC 207 contains a high-voltage currentsink MOSFET 216, a current-sense feedback (CSFB) circuit 217, and aprecision gate bias and control circuit 215 managed by microcontroller209 via control and interface 214. Microcontroller 209 also generatesthe time-based reference clocks Sync and Clk θ that are transmitted overlines 223 a and 223 b to facilitate waveform generation within channeldrivers 207 a through 207 n. CSFB circuitry 217 delivers a feedback andcontrol signal to SMPS 208 dynamically adjusting the +V_(LED) dependingon LED operating currents and requisite voltages.

One possible implementation of a system for phototherapy LED drive andcontrol 206 is illustrated in greater detail in FIG. 12 comprisingcontrol portion 207 z and channels a through n comprising channeldrivers 207 a through 207 n driving LED strings 205 a through 205 n,respectively, where the LED strings 205 a through 205 n may comprisedifferent types of LEDs having different constructions, dissimilarforward voltages, varying current demands, and emanating different EMRwavelengths λ₁, λ₂, λ₃, λ₄, etc. LED drivers 207 a through 207 n areformed on an LED driver IC 207 (FIG. 11), and each of the channeldrivers 207 a through 207 n and its associated LED string represents achannel. The number of channels “n” in the system or within a givendriver IC can vary from 1 to 64, with 8 to 16 channels per driver ICbeing preferable to minimize the number of components while reducing thepin count per IC. A phototherapy apparatus may also utilize more thanone driver IC per system. Further information regarding LED drive andcontrol circuitry is disclosed in U.S. Published Application Nos.2013/0082614 A1, 2013/0099681 A1, and 2013/0147370 A1, each of which wasfiled on Jan. 9, 2012, and each of which is incorporated herein byreference in its entirety.

To avoid uneven or irregular uniformity in brightness across an LED pad,in a preferred embodiment all “m” LEDs in any given one of LED strings205 a through 205 n comprise the same type and wavelength LEDs, selectedor sorted for having similar brightness at the same current. Formulti-string LED pads having varying types of LEDs in the same pad,strings of any given type and wavelength LED should in a preferredembodiment vary consistently over the n-channels in some regularperiodic fashion. For example, in a pad comprising LEDs havingwavelength spectra centered around λ₁, λ₂, and λ₃, channels 1, 4, 7, 10,13 and 16 (or alternatively a, d, g, j, m, and p) comprise strings of λ₁type LEDs, channels 2, 5, 8, 11, and 14 (alternatively as b, e, h, k,and n) comprise strings of λ₂ type LEDs, and channels 3, 6, 9, 12, and15 (alternatively as c, f, i, l, and o) comprise strings of λ₃ typeLEDs. In a four-wavelength pad, the LED drive system can be arranged inthe repeating sequence λ₁, λ₂, λ₃, λ₄, λ₁, λ₂, λ₃, λ₄, λ₁, and . . . .

The importance of repeating the LED sequence in regular intervals is toprovide the most uniform light distribution of any given wavelength LEDacross a pad without complicating the interconnecting wires to the LEDdriver IC. If all the like type LEDs were grouped together, e.g.channels 1 through 4 for λ₁ wavelength LEDs, channels 5 through 8 for λ₂type LEDs, etc., interconnection of driver IC 207 to the LED strings 205a through 205 n would require many jumpers or an expensive multilayerPCB to connect the LED driver IC to the LEDs.

Contrasting some significant differences between control and drive ofLEDs in HDTV backlighting and LED drive in LED phototherapy, the role ofthe microcontroller in HDTV backlight systems is to act an interpreter,a digital liaison, between the video scalar IC processing video imageinformation, and the backlight controller of the display. In videodisplays, the knowhow, proprietary algorithms and associatedIntellectual property reside in the graphics and video ICs, not in amicrocontroller. In fact, the product roadmap for these highlyintegrated circuits is eventually to eliminate the microcontroller inHDTVs altogether.

In the disclosed phototherapy apparatus, however, the patterns,algorithms, sequences and knowhow in the system for synthesizingwaveforms and frequencies used for driving arrays of different types ofLEDs is, in a preferred embodiment, not contained in a custom integratedcircuit, but instead is contained within the microcontroller or a easilyprogrammable logic device. Moreover, the ability to program andreprogram the controller is key to maintaining flexibility in a rapidlyevolving field. Such flexibility is not possible with dedicated andcustom integrated circuit systems and solutions. For example in thephototherapy system of FIG. 12, microcontroller 209 contains within itspattern library 210 a the waveform synthesis algorithms executed by LEDdriver IC 207. This waveform information generated by microcontroller209 is relayed from its internal bus interface 210 b to one or more. LEDdriver ICs, using a high-speed digital bus, in the example via serialperipheral interface (SPI) bus 213. While other digital interfaces maybe employed, the SPI bus has become an industry standard in LCD and HDTVbacklighting systems, and a common interface for LED driver ICs in largedisplays (but not in small displays used in handheld electronics).

Using the SPI protocol, each LED driver IC has its own unique chip IDcode. All data packets broadcast from microcontroller 209 on SPI bus 213include this unique chip ID in the header of the data stream as an atype of address—an address employed to direct the data to one and onlyone LED driver IC, i.e. the target LED driver IC. Only data matching aparticular chip ID will be processed by the corresponding target LEDdriver IC even though all driver ICs receive the same data broadcast.The chip ID is typically hardware-programmed for each LED driver IC withone or two pins on the IC. Using a four-state input where each pin canbe either grounded, tied to V_(logic), left open, or grounded through aresistor, a multistate analog comparator interprets the analog level andoutputs a 2-bit digital code. Using two pins, a 4-bit binary word (i.e.,a binary nibble) uniquely identifies one of 4² or 16 chip IDs. Whenevera data broadcast is received on SPI bus 213 matching the chip ID of anyspecific LED drive, i.e. the specific IC is “selected”, meaning theparticular LED driver IC responds to the broadcast instructions andsettings. Data broadcasts whose data header do not match a particularLED driver IC's chip ID are ignored. In summary, each LED driver 207comprising a set of “n” channel drivers is generally realized as asingle integrated circuit with its own unique “chip ID” used to directinstructions from the microcontroller 209 directly to that specific ICand to the channel drivers contained within it. The same communicationfrom microcontroller 209 is ignored by all other LED drivers made inintegrated circuits without the matching chip ID.

Within control portion 207 z of a selected LED driver IC, SPI interface220 receives the instructions from SPI bus 213 then interprets anddistributes this information to decoders 221 a through 221 n usinginternal digital bus 222 which instructs the individual channel driverson drive conditions (including channel by channel timing and LEDbiasing). For high-speed data transmission with a minimal number ofinterconnections, internal digital bus 222 comprises some combination ofserial and parallel communication. Since the bus is dedicated to the LEDdriver, such a bus may conform to its own defined standards and is notsubject to complying with any pre-established protocol.

This digital information from digital bus 222, once decoded by decoders221 a through 221 n, is next passed to digital data registers present inthe channel driver within each of channels a through n. For clarity ofidentification, respective elements within a given channel and itschannel driver utilize the same letter designator as the channel forexample, CSFB circuit 217 is labeled as 217 a in channel a and if shown,as 217 b in channel b, while counter 227 is labeled as 227 a in channela and if shown as 227 b in channel b. These registers may be realizedwith S-type or D-type flip-flops, static latch circuitry, or SRAM cellsknown to those skilled in the art.

In the particular driver IC shown, the decoded data for each channelincludes a 12-bit word defining the channel's on-time t_(on), a 12-bitword defining the phase delay φ, and an 8-bit word defining the LEDcurrent, stored respectively in t_(on) registers 224 a through 224 n, φregisters 225 a through 225 n, and I_(LED) registers 226 a through 226n. For example the decoded output of decoder 221 a comprising thet_(on), φ,and I_(LED) data for channel-a is loaded into registers 224 a,225 a, and 226 a, respectively.

The LED's on-time t_(on) along with the clock signals Clk θ and Synccombine to set the LED's brightness through its corresponding PWM dutyfactor D, and in waveform synthesis to set the frequency f_(synth) ofthe synthesized pattern of photoexcitation. Similarly, the decodedoutput of decoder 221 b comprising the t_(on), φ, and I_(LED) data forchannel-b is loaded into registers 224 b, 225 b, and 226 b respectively,and the decoded output of decoder 221 n comprising the t_(on), φ, andI_(LED) data for channel-n is loaded into registers 224 n, 225 n, and225 n respectively.

These data registers may operate as clocked latches loading data only atpredefined times, e.g. whenever a Sync pulse occurs, or may be changedcontinuously in real-time. Synchronizing the data loading and executionto a clock is known herein as “synchronous” or “latched” operation whileoperating the latches and counter where the data can be changeddynamically at any time is referred to as “asynchronous” or“non-latched” operation. Latched operation limits the maximum operatingfrequency but exhibits greater noise immunity than asynchronousoperation. In this invention disclosure, waveform synthesis performed bychannel drivers 207 a through 207 n integrated into an IC labeled as LEDdriver IC 207 under the control of microcontroller 209 can be realizedby either method—using either latched or asynchronous methods. Indisplay applications, however, only latched operation is employedbecause of an LCD image's severe sensitivity to noise.

In non-latched or asynchronous operation, the data received over SPI bus213 is decoded and immediately loaded into the t_(on), φ, and I_(LED)registers 224 a through 224 n, 225 a through 225 n, and 226 a through226 n, Depending on the LED driver IC's implementation, two possiblescenarios can occur thereafter. In the first case the count beingexecuted in any given one of counters 227 a through 227 n is allowed tocomplete its operation, then the new data is loaded into the counter andthe new count commences.

By example, in non-latched operation data freshly loaded from decoder221 a into t_(on), φ, and I_(LED) registers 224 a, 225 a, and 226 awould wait until the count in counter 227 a is completed. After thecount is completed the updated data for t_(on) and φ in registers 224 aand 225 a are loaded into counter 227 a and simultaneously the updatedI_(LED) data in register 226 a is loaded into D/A converter 228 achanging the bias condition on precision gate drive circuit 215 a. Afterloading the data, counter 227 a commences immediately counting pulses onthe Clk θ line 223 b, first by turning off LED string 205 a if it wason, then counting φ number of pulses in data register 225 a beforetoggling precision gate bias and control circuit 215 a and MOSFET 216 aback on. After turning LED string 205 a back on, counter 227 a thencounts t_(on) number of counts loaded from register 224 a on Clk θ line223 b before shutting LED string 205 a off again. The counter 227 a thenwaits for another instruction.

In the second alternative for non-latched or asynchronous operationbehaves exactly the same as the non-latched operation describedpreviously except that whenever an instruction is received via abroadcast on SPI bus 213, the latch is immediately rewritten andsimultaneously restarted. Other than cutting short the ongoing countcycle at the time the register data was rewritten, the operatingsequence is identical. Regardless of which asynchronous method is used,it takes time to broadcast, decode, and commence operation for each andevery channel on a one-by-one basis. In display applications, the delayin writing new data (and changing an LED string's operating conditions)between the first and last channel of an LCD panel may result in flickerand jitter. As such, asynchronous operation is not a viable option inLCD backlighting. In LED phototherapy, however, where a fixed conditionmay be maintained for minutes, non-latched operation is a viable optionespecially for generating higher frequency LED excitation patterns, i.e.for higher values of f_(synth).

Unlike in asynchronous operation, where data is updated continually, inlatched or synchronous operation LED operating conditions are updatedonly a predetermined occasions, either synchronized to fixed times, orprescribed events. In latched operation of the circuit shown in FIG. 12,whenever the Sync pulse occurs on line 223 a, the data most recentlyloaded into t_(on) register 224 a and φ register 225 a is loaded intocounter 227 a. Counter 227 a then commences counting the number of phasedelay pulses on the Clk θ line 223 b before toggling precision gate biasand control circuit 215 a on. After completing the count, the countertoggles on precision gate bias and control circuit 215 a, biasing thegate of current sink MOSFET 216 a to conduct a prescribed amount ofcurrent I_(LED) thereby Illuminating LED 205 a to desired level ofbrightness. Counter 227 a subsequently counts the number of Clk θ pulsesloaded from t_(on) resister 224 a until the count is complete, and thentoggles precision gate bias and control circuit 215 a to shut offcurrent MOSFET 216 a and terminate illumination. At this point,depending on the LED driver IC's design, LED 205 a may remain off forthe remainder of the T_(sync) period, i.e. until the next Sync pulseappears on line 223 a, or alternatively repeatedly toggle on and off atthe value loaded into duty factor register 224 a until the next Syncpulse occurs on line 223 a.

On the same T_(sync) pulse, the data most recently loaded into t_(on)register 224 b and φ register 225 b is loaded into counter 227 b.Counter 227 b counts the stored number of phase delay pulses φ occurringon the Clk θ line 223 b before toggling precision gate bias and controlcircuit 215 b on, biasing the gate of current sink MOSFET 216 b toconduct a prescribed amount of current I_(LEDb), thereby illuminatingLED 205 b to desired level of brightness. Counter 217 b subsequentlycounts the number of Clk θ pulses loaded from t_(on) resister 224 buntil the count is complete, and then toggles precision gate bias andcontrol circuit 215 b to shut off current MOSFET 216 b and terminateillumination. At this point, depending on the LED driver IC's design,LED string 205 b may remain off for the remainder of the T_(sync)period, i.e. until the next Sync pulse appears, or alternativelyrepeatedly toggle on and off at the value loaded into duty factorregister 224 b until the next Sync pulse occurs. A similar processoccurs for all n-channels of the LED driver IC.

In latched systems the Sync pulse serves several purposes. First it isan instruction to load the data from the t_(on) and φ registers 224 athrough 224 n and 225 a through 225 n into the corresponding one ofprogrammable digital counters 227 a through 227 n. Second it is aninstruction to reset the counter and commence counting, first to pass aperiod of time for phase delay φ, and then to turn on the LED string forthe number of clock counts loaded into the corresponding t_(on) register224 a through 224 n. Thirdly, it is an instruction to load the value inthe I_(LED) register 226 a through 226 n into the corresponding D/Aconverter 228 a through 228 n, precisely setting the analog value ofconduction current for that specific channel whenever it is toggled on.Finally it prevents noise from overwriting the data in the data registermidstream jumbling the count.

Also triggered by the Sync pulse in latched operation, the bit dataloaded into I_(LED) register 226 a is simultaneously interpreted by D/Aconverter 228 a to set the reference current αI_(ref) feeding precisiongate bias and control circuit 215 a. This reference current sets theanalog magnitude of LED current I_(LED1) flowing in MOSFET 216 a and inLED string 205 a whenever the particular channel is toggled on andconducting. It has no bearing on the MOSFET's current when counter 227 atoggles the particular 207 a channel off. The same process occurssimultaneously for all n channels, i.e. for channel drivers 207 athrough 207 n.

The value of reference current αI_(ref) in any given channel driver isset in two ways. Firstly, a single precision trimmed voltage referenceV_(ref) present in channel drivers 207 a through 207 n along with aprecision resistor R_(set) (not shown) sets the value of I_(ref). Theresistor R_(set) may be integrated provided that it is trimmed forabsolute accuracy during manufacturing, or may comprise a discreteprecision resistor, externally connected to the IC that contains LEDdrivers 207 a through 207 n. This single reference current is thenmirrored to every channel a through n, and as needed may be furthertrimmed for improved channel-to-channel matching. Secondly, a digitallycontrolled multiplier α sets the current in each of channels a through nin accordance with the 8-bit word loaded into the corresponding one ofI_(LED) registers 226 a through 226 n and interpreted by a correspondingone of D/A converters 228 a through 228 n.

For example in channel driver 207 a in channel a, the 8-bit word storedin I_(LED) register 226 a is converted into one of 256 levels for themultiplier α, allowing the current in MOSFET 216 a and in LED string 205a to be set anywhere from 0% to 100% ·I_(ref) in 256 steps, i.e. Inincrements of 0.39% per step whenever MOSFET 216 a is on and conducting.The same operation occurs in each of channel drivers 207 b through 207n, enabling digital control of LED current in every LED string 205 athrough 205 n via SPI bus 213.

It should be noted that in an LED backlit HDTV, it is preferable tochange LED brightness using PWM dimming rather than by changing thevalue of the LED current because the color temperature of white LEDs isa function of current. This consideration is not a concern in thedisclosed LED phototherapy apparatus. In fact, in LED phototherapyeither LED current, PWM brightness control, or a combination of both maybe used to set LED brightness. In a preferred embodiment of thisinvention, however, LED brightness is also set by PWM brightnesscontrol, not for purposes of maintaining color temperature of LEDs, butprimarily so that the control of LED current can be used for otherpurposes, specifically for improving safety and facilitating better LEDuniformity across a pad. These features in the disclosed invention aredescribed later in this disclosure.

The ability to intelligently and dynamically regulate LED voltage toinsure proper biasing of every LED string is another important elementof the disclosed phototherapy apparatus. The forward voltage of an LEDstring varies both with its construction and its current. Since LEDshaving different wavelengths require unique and differing construction,their forward voltages are unlikely to match one another as illustratedin the example of FIG. 13.

Defining V_(λ1) as the mean voltage across a string of LEDs emitting awavelength λ₁, V_(λ2) as the mean voltage across a string of LEDsemitting a wavelength λ₂, and V_(λ3) as the mean voltage across a stringof LEDs emitting a wavelength λ₃, and assuming natural variability inmanufacturing leads a random (i.e. Gaussian) distribution in forwardvoltage around its mean of ±ΔV_(f) for LEDs of any given wavelength,then a LED driver used in phototherapy must be able to consistentlydrive a population of LED voltages comprising the set V_(λ1)±ΔV_(f),V_(λ2)±ΔV_(f) and V_(λ3)±ΔV_(f). If we furthermore arbitrarily defineV_(λ2)>V_(λ1)>V_(λ3), then a SMPS must provide a voltage +V_(LED) higherthan the highest LED string voltage, mathematically as+V _(LED)>(V _(λ2) +ΔV _(fe))>V _(λ2)>(V _(λ3) −ΔV _(fe))

Since the highest voltage string is not known a priori, the LED driverIC must be capable of identifying the highest string voltage and todynamically adjust the LED supply voltage +V_(LED) to a voltage slightlyhigher than that voltage. Because all the LED strings share a commonanode, the LED string with the highest forward drop V_(f) naturallyexhibits the lowest voltage at the cathode of the final LED in thestring, i.e. the voltage on the drain of its current sink MOSFET. Eachof CSFB circuits 217 a through 217 n passes the lower of the voltage atits input terminal or the voltage on the drain of the correspondingcurrent sink MOSFET in the channel to its output.

As illustrated in FIG. 13, the CSFB circuits are connected in daisychain fashion, i.e. in series “head to toe”, with the input to CSFBcircuit 217 d coming from the output of CSFB circuit 217 e, the input toCSFB circuit 217 e coming from the output of CSFB circuit 217 f, and soon. The first CSFB 217 n in the chain (not shown) has its input tied tothe supply voltage V_(driver) so as to not limit the range of the+V_(LED) output. The last CSFB circuit 217 a in the daisy chain (notshown in FIG. 13) drives the input to SMPS 208 ultimately controllingthe supply output voltage +V_(LED).

In the example shown in FIG. 13, the output of CSFB circuit 217 goutputs a voltage (V_(LED)−V_(λ2)). CSFB circuit 217 f compares thisvoltage against the drain voltage of the MOSFET 216 f in channel driver207 f, namely (V_(LED)−V_(λ3)) but since V_(λ2)>V_(λ3) then(V_(LED)−V_(λ3))>(V_(LED)−V_(λ2)) so CSFB circuit 217 f outputs thelower voltage, namely (V_(LED)−V_(λ2)). In the next downstream channel,CSFB circuit 217 e compares its input (V_(LED)−V_(λ2)) against the drainvoltage of the MOSFET 216 e in channel driver 207 e, namely(V_(LED)−(V_(λ2)+ΔV_(fe))) but since (V_(λ2)+ΔV_(fe))>V_(λ2) thenaccordingly (V_(LED)−V_(λ2))>(V_(LED)−(V_(λ2)+ΔV_(fe))) so CSFB circuit217 e outputs the lower voltage, namely (V_(LED)−(V_(λ2)+ΔV_(fe))). Thisprocess continues until CSFB circuit in the last channel (channel a)outputs a voltage to the negative input terminal of SMPS 208. If thenegative feedback voltage is decreased, the SMPS 208 responds byincreasing its +V_(LED) output. Since the daisy chain of CSFB circuits217 a through 217 n in channels a through n outputs the lowest channelvoltage (regardless of the order in which the CSFB circuits areconnected) then the +V_(LED)=f(CSFB) will automatically adjust to supplythe minimum needed voltage to power the highest voltage LED string, evenif the LEDs are not running at the same currents.

Controlling which channels are conducting is simply a matter of loadingthe specific register the appropriate data. There are three ways to turnoff the current in any given channel in an LED driver IC. First, someLED-driver-ICs have a digitally controlled toggle register to make itconvenient to turn a channel on and off independent of its value of D orof its current αI_(ref). Second, the channel to be turned off can beloaded with an on time t_(on)=0. Third, the channels to be biased offhave their I_(LED) data register 231 set for α=0.

The third case is shown in FIG. 14A where only the λ₂ channels 207 b,207 e, 207 h, 207 k, and 207 n are illuminated with a setting of α>0,e.g. at 50%. All other channels have I_(LED)=0 and therefore α=0. Theanalog parameter I_(ref) is biased to a value V_(ref)/R for allchannels, the on time t_(on) is equal to the full period T_(sync) (i.e.D=100%), and the phase delay φ is set globally to zero. The current inevery one of the five on-channels is then αI_(ref). To power the arrayof λ₂ LEDs, +V_(LED) outputs a voltage V_(λ2)+ζ where ζ the extravoltage above V_(λ2) needed to insure the current sink circuit operatesproperly. All these parameters except for I_(ref) (which is set by ananalog voltage and a resistance) are programmed through data registers221 a through 221 p contained within the channel decoder circuitry.

FIG. 14B illustrates that by rewriting the data in registers 221 athrough 221 p the wavelength LEDs being illuminated can easily bechanged. In this case I_(LED) register data 231 is changed so thatchannels 207 a, 207 d, 207 g, 207 j), 207 m, and 207 p are set to avalue I_(LED)>0 (and therefore α>0), e.g. at 50%, and other channels areset to I_(LED)=0 (and α=0). As previously described, the analogparameter I_(ref) is biased to a value V_(ref)/R for all channels, theon-time t_(on) is fixed at the full period T_(sync) (where D=100%) andthe phase delay φ is set globally to zero. The current in every one ofthe six on-channels is then αI_(ref). To power the array of λ₁ LEDs,+V_(LED) outputs a voltage V_(λ1)+ζ where ζ is the extra voltage aboveV_(λ1) needed to insure the current sink circuit operates properly.

Ideally, in order to minimize BOM (build of material) costs by takingadvantage of economies of scale of semiconductors used in high volumeconsumer and computing products, the hardware components in a medicalphototherapy apparatus can share certain components and ICs with that ofLED drivers designed for computer and HDTV backlights. That said, theoperating voltages, currents, power levels, heat dissipationconsiderations, circuit board form factors, passive component selection,and interconnect routing of a computer monitor or HDTV screen arecompletely different than what is needed in a phototherapy apparatus.

Moreover, in operation, the functions, firmware and software for amedical phototherapy apparatus are completely different from those forHDTV and necessarily address dissimilar issues. One key difference inthe purpose of PWM control of LED currents in a HDTV is to facilitatebrightness control, either globally (across a screen), or locally (in aportion of the screen), and to synchronize the timing of backlight drivecircuitry to that of the video image to avoid aliasing, flicker,pixilation, image blur, and other visual and psycho-optical effects. Bycontrast, in phototherapy, the purpose of PWM control of LED current isto sequence multiple LED wavelengths while performing waveform synthesis(including both frequency and brightness control).

Programmable Waveform Synthesis

As explained previously, the control variables used in phototherapy arecompletely different from those used in displays. In an LCD backlightingapplication, the duty factor D is used only to facilitate brightnesscontrol in a backlight operating at a fixed frequency, essentiallysetting the percent of each Vsync period the LEDs should be Illuminated.The phase delay is used to compensate for signal propagation delaysacross large area LCD panels. Moreover, in displays, the Vsync periodand hence the system's governing operating frequency is fixed. The Vsyncpulse maintains a constant rate for the entire HDTV system duringoperation, for the video image refresh, for every LED driver IC withinthe backlight system, and for every channel within a driver IC. In LCDdisplays only certain fixed frequencies and integers multiples thereofare used, e.g. 60 Hz, 120 Hz, 240 Hz, and possibly 480 Hz. While theseset frequencies may be user selectable at setup, they remain fixedduring use.

In the disclosed invention for phototherapy, however, the variablet_(on) along with the clock signals Sync and Clk θ operate atdynamically varying frequencies, not at fixed frequencies, operating inconcert to perform independent waveform synthesis for each channelsetting both the photoexcitation pattern's frequency f_(synth) andbrightness.

For example, in FIG. 15A, three different-frequency LED excitationpatterns 241, 242, and 243 are synthesized from a single clock 180generated from microcontroller 209, all with a resulting duty factorcontrolled brightness of 50%. As shown, pulses from clock Clk θ repeatwith period T_(θ), for example at 9.346 kHz and a corresponding periodT_(θ)=107 μsec. In digitally synthesized waveform 241, an array of LEDsof wavelength λ is turned on for 16 clock pulses (by programming the ontime t_(on)=16) and then subsequently turned off. If a 12-bit counter isemployed, the full count for the counter is 4096 clock pulses, which atthis clock frequency corresponds to maximum period ofT_(cntr)=4096·0.107 msec=438 msec meaning that without intervention fromthe microcontroller, the array of LEDs would remain off for another 4080pulses after being on for only 16 pulses. At full count, the resultingfrequency of the counter's output would be f_(cntr)=2.28 Hz.

Rather than letting the clock run to its full count of 4096, instead, attime t=32 pulses (only 16 pulses after the LEDs shut off) the cycle isforced to repeat. Forcing a shorter period can be accomplished inseveral ways. In asynchronous (non-latched) mode, the registers can bewritten by the SPI bus after the 31^(st) clock pulse but before the32^(nd) pulse. Since the SPI bus can broadcast data at 10 MHz and eachclock pulse lasts 107 μsec, there is plenty of time to change theregister data to terminate on the 32^(nd) pulse. Only the specificchannel is affected.

If more than one channel requires resetting and restarting itscorresponding counter, each channel must be instructed via the SPI busone-by-one. Alternatively, in latch (synchronous) mode, the count can berestarted by a Sync pulse after the 31^(st) clock pulse but before the32^(nd) pulse. On the 32^(nd) pulse, the sequence will naturally restartits count on this channel and every other channel that is biased into anon state (i.e. where t_(on)>0 and I_(LED)>0). Unless the data in thet_(on), φ, and I_(LED) registers is changed prior to the Sync pulse, theprior data will be loaded into the counter and the last cycle repeated.If new data is loaded, the new data will take effect synchronous to theSync pulse.

The resulting synthesized waveform is a square wave where an array ofLEDs of wavelength λ conducts for 16 clock pulses and is off for 16pulses. The synthesized waveform 241 therefore has a period of 32 clockpulses or nT_(θ)=32·0.107 msec=3.424 msec with a corresponding frequencyf_(synth1)=1/nT_(θ)=292 Hz.

Because the on time and off time are equal, i.e. t_(on)=t_(off), and theperiod T_(synth)=t_(on)+t_(off) then the synthesized duty factor isgiven byD=t _(on) /T _(synth) =t _(on)/(t _(on) +t _(off))=t _(on)/2t _(on)=50%

So even though the t_(on) register was programmed for only 16 pulsescorresponding to a duty factor of D=16/4096=1/256=0.39% for a 12-bitcounter at its full count of 4096 (with a corresponding frequencyf_(cntr)=2.28 Hz), because the counter was restarted at t=32 pulses, theresulting duty factor and frequency are 128 times higher, i.e. 50% and292 Hz.

Note that in latched operating mode, the Sync pulse must occur at afrequency equal to or higher than the frequency of the waveform beingsynthesized, i.e. T_(sync)≦nT_(θ) or as expressed by the frequencyrelation f_(sync)>f_(synth). If this criterion is not met, there is noway to update the data registers in time to force the counterretriggering to meet the specified synthesized frequency.

Electrically, the synthesized frequency f_(synth1)=292 Hz correspondsclosely to the musical note D above middle C in the audio spectrum, orD⁰. As described previously, the natural operating frequency of manyorgans and tissue such as the heart, lungs, intestines, nerves and thebrain, the maximum data rate for vision and hearing, along with manymolecule vibrations all occur in the audio and subsonic spectrum offrequencies, mostly under a few kilohertz and some as low as one hertz.Even though the synthesized frequency is manifested as repeating seriesof light pulses and not as sound, the impinging light energy is absorbedand redistributed into molecules and tissue at the same frequency,leading to a physical response in kinetic and potential energysynchronous to audio spectra. As such, it is convenient, if notinsightful, to use music notation to describe the synthesizedphotoexcitation waveforms musically as notes chords rather thanmathematically as Fourier series and transformations.

In digitally synthesized waveform 242 of FIG. 15A, an array of LEDs ofwavelength λ is turned on for 8 clock pulses (by programming the on-timesetting to t_(on)=8) and then subsequently turned off. If a 12-bitcounter is employed, the full count for the counter is 4096 clockpulses, which at this clock frequency corresponds to maximum period ofT_(cntr)=4096·0.107 msec=438 msec meaning that without intervention fromthe microcontroller, the array of LEDs would remain off for another 4088pulses after being on for only 8 pulses.

Rather than letting the clock run to its full count, instead, at timet=16 pulses (only 8 pulses after the LEDs shut off) the cycle is forcedto repeat. As in waveform 241, forcing a shorter period can beaccomplished in several ways. In asynchronous (non-latched) mode, thedata registers can be written by the SPI bus after the 15^(th) clockpulse but before the 16^(nd) pulse. Since the SPI bus can broadcast dataat 10 MHz and each clock pulse lasts 107 μsec, there is plenty of timeto change the register data to terminate on the 16^(th) pulse. Only thespecific channel is affected.

If more than one channel requires resetting and restarting itscorresponding counter, each channel must be instructed via the SPI busone-by-one. Alternatively, in latch (synchronous) mode, the count can berestarted by a Sync pulse after the 15^(th) clock pulse but before the16^(th) pulse. On the 16^(th) pulse, the sequence will naturally restartits count on this channel and every other channel that is biased into anon state (i.e. where t_(on)>0 and I_(LED)>0). Unless the data in thet_(on), φ, and I_(LED) registers is changed prior to the Sync pulse, theprior data will be loaded into the counter and the last cycle repeated.If new data is loaded, the new data will take effect synchronous to theSync pulse.

The resulting synthesized waveform is a square wave where an array ofLEDs of wavelength λ conducts for 8 clock pulses and is off for 8pulses. The synthesized waveform 242 therefore has a period of 16 clockpulses or as nT_(θ)=16·0.107 msec=1.712 msec with a correspondingfrequency f_(synth2)=2/nT_(θ)=584 Hz. The resulting waveform has afrequency exactly double that of the prior example wheret_(on)=t_(off)=16 pulses, so that f_(synth2)=2f_(synth1)=584 Hz. Sincef_(synth1) was synthesized to oscillate at an audio spectrum frequencycorresponding to the musical note D above middle C, or D⁰, then atdouble that frequency f_(synth2) also oscillates at the musical note“D”, except one octave higher than middle C. i.e. D¹.

Waveform 243 illustrates synthesis of a photoexcitation pattern having afrequency four times that of waveform 241, or as f_(synth3)=4f_(synth1).As such, the on-time t_(on) is set to 4 clock pulses and the counter isreset at 8 clock pulses. The resulting synthesized waveform is a squarewave where an array of LEDs of wavelength λ conducts for 4 clock pulsesand is off for 4 pulses. The synthesized waveform 243 therefore has aperiod of 8 clock pulses or as nT_(θ)=8·0.107 msec=0.856 msec with acorresponding frequency f_(synth3)=4/nT_(θ)=1,168 Hz, corresponding tothe musical note D two octaves above middle C, or D².

Summarizing the synthesized waveforms Table 1 illustrates that a 12-bitcounter and 9.346 kHz clock can algorithmically synthesize a wide rangeof frequencies by resetting the programmable counter at the appropriatetime, i.e. so T_(reset)≦T_(synth) where the reset may occurasynchronously through the SPI bus or synchronously using the Tsyncpulse. By extrapolation f_(synth4) and f_(synth5) were generated bydoubling and quadrupling the period of the 292 Hz D⁰ waveform-synthesis,resulting in 146 Hz and 73 Hz frequencies corresponding to the musicalnotes D one octave and D two octaves below middle C, i.e. D⁻¹ and D⁻².

TABLE 1 Algorithmically synthesized waveforms f_(synth) Clock θ CounterD_(entr) T_(reset) T_(synth) (note) D_(synth) Name 9.346 12 bit 64 12813.696 ms  73.0 Hz 50% f_(synth5) kHz 4096 step (D⁻²) T = f = 32 64 6.848 ms   146 Hz 50% f_(synth4) 107 μs 2.28 Hz (D⁻¹) T = 16 32  3.424ms   292 Hz 50% f_(synth1) 438 ms (D⁰) 8 16  1.712 ms   584 Hz 50%f_(synth2) (D¹) 4 8  0.856 ms 1,168 Hz 50% f_(synth3) (D²)

The disclosed method to algorithmically synthesize waveforms ofdifferent frequencies can be adapted to the previously disclosedphototherapy sequential waveform synthesis algorithm 170 shown in FIG.10A simply by changing the channels being driven from those controllingLEDs with λ₂ wavelengths, to those channels controlling LEDs with λ₁wavelengths as illustrated previously in FIG. 14A and FIG. 14B. Theresulting output of the LED pad using multiple wavelength LEDs at afixed brightness and photoexcitation frequency is illustrated inwaveform 245 of FIG. 15B where an array of LEDs at λ₂ wavelengths drivenat a PWM brightness of 50% and frequency f_(synth) changes at time t₁into an array of LEDs at λ₁ wavelengths driven at a PWM brightness of50% and the same frequency f_(synth) changes.

In an alternative embodiment the synthesized frequency and the LEDwavelength can both be changed dynamically as illustrated in waveform246 of FIG. 15B. In this example an array of λ₂ wavelength LEDs drivenat a PWM brightness of 50% and frequency f_(synth1) changes at time t₁into an array of LEDs at λ₁ wavelengths driven at a PWM brightness of50% but at a different frequency f_(synth2). As illustrated thefrequency given by f_(synth1)=1/nT_(θ) and the frequency given byf_(synth1)=1/mT_(θ) are different simply because m≠n, without requiringany change in the frequency of clock Clk θ.

It is also possible to excite different strings of LEDs, e.g. of thesame wavelength, at different photoexcitation frequenciessimultaneously, i.e. to synthesize f_(synth1) and f_(synth2)concurrently, a method referred to herein as “harmonizing”, i.e. formingharmonic frequency multiples through waveform synthesis. For example, agiven therapy may find efficacy is improved in two frequencies such asD⁰ and D¹ are used together. It should be mentioned that mixing multiplesynthesized photoexcitation frequencies together (“harmonizing”) isdifferent that concurrently illuminating tissue with differentwavelengths of light (“blending”) discussed and summarized previously inFIG. 9E. While the concept of multiple co-synthesis of photoexcitationfrequencies may appear obvious if not trivial, using the hardware of LEDdriver ICs the task is not straightforward.

Referring once again to Table 1 and FIG. 15A, recall that if a range ofwaveform frequencies is synthesized on different channels concurrentlyusing latched mode operation, the rule that the reset pulse must beequal to (or faster than) the synthesized frequency applies to thehighest synthesized frequency. For example if one channel synthesizes584 Hz signal f_(synth2) shown by waveform 242, then the counter ofevery channel will necessarily be reset by T_(sync) at time t=16, 32, 48. . . pulses, forcing every channel to reload their corresponding dataregisters and restarting their counts. This requirement to reset thecounter every 16 pulses, i.e. at a frequency of 584 Hz or faster,remains in effect so long that f_(synth2) is the highest frequency beinggenerated. If alternatively an even higher frequency such asf_(synth3)=1.168 Hz is synthesized, the Sync pulse must occur at even ahigher frequency, at least as fast as the synthesized frequency, meaningin the minimum 1/T_(sync)>f_(synth3).

Every time a Sync pulse occurs, any channel switching at a lowerfrequency must be restarted in a manner that preserves its present countvalue, meaning it must be restarted with new t_(on) and φ to continuedoing what it was doing until its programmed period is completed.Specifically any channel still on and conducting should be restarted inthe on condition with a on-time t_(on) loaded into the counter equalingthe intended on-time less the number of counts that already occurredwith that channel on. Likewise any channel already having completed itscount, off and non-conducting should be restarted in the off conditionwith a phase delay φ loaded into the counter equaling the intendedoff-time less the number of counts that already occurred with thatchannel off.

This multi-frequency drive requirement for synchronous mode waveformsynthesis example is clarified in FIG. 16, where the highest frequencysynthesized waveform 243 has a frequency f_(synth3) four times higherthan that of f_(synth1) waveform 241, i.e. the period of waveform 241 isnT_(θ), and where the shorter period of waveform 243 has a periodnT_(θ)/4. As shown in waveform 180, clock Clk θ has in this example afixed frequency 1/T_(θ). If we assume the aforementioned values whereclock Clk θ has a frequency of 9.346 kHz and a period T_(θ)=107 μs,where f_(synth1)=292 Hz and where f_(synth3)=1,168 Hz, then the Syncpulse 253 must occur at a frequency no slower than 1,168 Hz, i.e. every8 clock pulses (0.856 msec). Since the Sync pulses occur every8-clock-pulses, on pulses 8, 16, 24, 32 . . . then the register data forthe synthesis of f_(synth1) waveform 241 requires updating with everySync pulse.

As shown in FIG. 16, at the onset, i.e. at time t₀, the register datafor waveform 241 is loaded as t_(on)=16 and φ=0, meaning the LED stringturns on immediately and will stay on for 16 pulses unless interrupted.When the next Sync pulse occurs at time t₁, not only is the registerdata for waveform 243 necessarily updated but so is waveform 241 aswell, being loaded with data t_(on)=8 and φ=0 since the channel wasintended to be on for 16 pulses and 8 pulses have elapsed, leaving 8more to go. Actually any value of t_(on) equal to or greater than 8would work equally well (since the channel will be forced off at t₂anyway) but for programming purposes it is convenient to keep track ofthe remaining conduction time, especially for when PWM brightnesscontrol is invoked and t_(on)≠t_(on). At time t₁ it is important tomaintain φ=0; otherwise the LEDs for the affected channels would turnoff at the time of the Sync pulse.

Later, at time t₂ when the next Sync pulse occurs, the register data forwaveform 241 is again updated, this time turning off the channel withthe settings t_(on)=0 and φ=0 or 16. Setting t_(on)=0 forces the channeloff regardless of the value phase delay φ.

Although not preferred, in an alternative approach the phase delay φ canbe used to keep the channel off, e.g. setting φ≧8 delays it from turningon before the next Sync pulse occurs even if t_(on)>0. Eight clockpulses later, at time t₃ the channel must once again be kept offinsuring the register data is loaded with t_(on)=0. Although the channelcan also be kept off by setting φ≧8, in a preferred embodiment thechannel is kept off by maintaining t_(on)=0, reserving the phase delayfeature for another purpose and not dedicated to performing waveformsynthesis.

In manner prescribed, the simultaneous synthesis of two waveforms 241and 243 having dramatically different frequencies f_(synth1) andf_(synth3) can be achieved even when using synchronous, i.e. latch mode,operation. So by the judicious choice of the values of on-time t_(on),phase delay φ, and the forced timing of the Sync pulse, synchronous modeoperation can achieve synthesis of any number of square wave and pulsedphotoexcitation waveforms up to a frequency limited by the maximumoperating rate of the LED driver ICs. Usually this restriction occursbecause of the maximum rate of Clk θ clock 180 used for counting pulses,and not by the maximum frequency of the Sync pulse Itself.

For example in FIG. 12, the LED driver IC 207 includes t_(on) and φregisters employing a 12-bit register and counter. For latched operationat maximum resolution, Clk θ should be 4096 times faster than the Syncpulse rate, regardless of the elapsed time (in milliseconds) of periodT_(sync). At a fixed clock rate operating at the full count on thecounters 227 a through 227 n, the meaning of the number stored in thet_(on) registers divided by 4096 truly represents the duty factor of thecounter D_(cntr)=t_(on)/T_(sync). This duty factor D_(cntr) defines upto 4096 increments of LED on time per Sync period, and the phase delay φdefines up to 4096 increments of the turn-on delay time in any givenSync period when the LED first turns on.

Since Clk θ normally runs 4096 times faster than the Sync pulse rate,i.e. where f_(θ)=4096/T_(sync) the fastest circuit (and therefore thefunction most likely to limit the speed of operation) is the maximumfrequency which the counters can count accurately. Synthesizing theaforementioned f_(synth3) waveforms at 1,168 kHz requires that Syncoperate at the same speed, and since Clk θ must run a frequency 4096times higher, then f_(θ)=4096/T_(sync)≧4096·f_(synth)=4.784 MHz, a muchhigher speed than required in most display applications. As mentionedpreviously, the highest Vsync refresh rate used in high-end HDTVs is 480Hz and many can't even operate beyond 240 Hz. If a LED driver IC isdesigned to work only up to this Vsync refresh rate 480 Hz, it meansf_(θ) operates a maximum rate just beyond 1.97 MHz, e.g. 2 MHz.

To overcome this limitation without the need to redesign the LED driverIC or develop custom ICs, the microcontroller program can be altered togenerate a 10-bit clock for counting rather than 12-bits. Since thecounter performing PWM control and dimming is designed for operationwith 12-bits of resolution, i.e. 4096 increments of time and dutyfactor, it is not obvious to drive a 12-bit counter with a 10-bit clock,one where f_(θ)=1024/T_(sync). But as illustrated previously in thisdisclosure, in the phototherapy application frequency synthesis is thekey parameter, not precision brightness control. Since the Sync pulsecuts short the full count, this precision of brightness control is notutilized anyway. In such a case, operating at a clock rate 1024 timesthat of the Sync pulse expands the range of waveform synthesis to higherfrequencies.

For instance a 2 MHz clock using synchronous mode operation with 12-bitsof precision is shown previously only able to synthesize digital (pulse)waveforms up to 480 Hz. Using 10-bits of precision in the same controlscheme increases the maximum synthesized frequency by 4×, from 480 Hz to1.92 KHz, enough to synthesize frequencies equivalent to the musicalnote D² (and beyond). The frequency demands for sine wave synthesis arehowever more stringent and beyond the scope of this disclosure.

Another method is to run Clk θ at its maximum possible rate and togenerate the Sync pulse independently of Clk θ except that the Syncpulse should be forced to occur on the rising edge the next availableClk θ pulse using an AND gate, a one shot monostable multivibrator, or asimple PLL (phase locked loop). The synchronized versions of the Syncand Clk θ signals are then broadcast to the LED driver ICs on clocklines 223 a and 223 b, respectively, except unlike in previouslydescribed cases wherein the two clock signals operate with a fixedratio, in this embodiment they do not.

If even higher synthesized frequencies of square wave pulses aredemanded, high-speed clock circuitry may be utilized, or alternativelylatched (synchronous) operation can be replaced by non-latched(asynchronous) operation.

Asynchronous operation is similar to latched mode except that thecounter's count must be reset each time the data registers are loaded bythe SPI bus. Without the frequencies limitation of data updates, themaximum frequency that can be algorithmically synthesized by the systemof FIG. 12 is practically limited to waveform 247, having a frequencyequal to one-half that of the rate of clock Clk θ, as shown in FIG. 15C.For example if Clock 180 is operating at a frequency of f_(θ)=1/T_(θ),then the limit of the synthesized frequency is then limited tof _(synth)≦0.5f _(θ)=1/2T _(θ)

For example, a 2 MHz can generate a synthesized pulse frequency of 1 MHzas shown in waveform 247, switching at time t₁ from an array of LEDswith λ₂ wavelengths to an array of LEDs with λ₁ wavelengths withoutinterruption. Such rapid changes are made possible by the high bandwidthcapability of the SPI bus, able to send data at a clock rate of 10 MHzor 0.1 μsec. The clock period of a 2 MHz clock is T_(θ)=0.5 MHz, fivetimes slower than the SPI bus. Ideally for operation at such high ratesthe counters could be redesigned to “set and forget,” meaning that oncethe condition is written into the counter, it keeps resetting andrestarting after each clock cycle is completed. But as any synthesizedfrequency approaches the clock frequency only 50% is possible with anydegree of consistency.

It should be noted that at this time there is no known reason tosynthesize photoexcitation frequencies above a few kilohertz.Nonetheless waveform 180 represents the upper end in the range offrequency synthesis using the described hardware. Power dissipation atthe maximum clock rate however can be significant Under normaloperation, synthesis of lower frequencies doesn't require such a fastclock continuously. Switching the clock to a high frequency only whenrequired as shown at time t₁ in waveform 251 of FIG. 15D saves powerexcept when the performance is needed. The same dynamic frequencyswitching of Clk θ can be used whenever high frequency waveforms must besynthesized, and a slower clock rate for Clk θ employed under normalcircumstances.

While such methods are important in extending operation of aphototherapy apparatus to the highest possible frequencies, synthesizingextremely low frequencies using purely hardware implementations canlikewise be problematic, requiring counters with a high number of bitsconsuming large silicon areas.

The practical limit of the LED driver IC by itself is set by the countersize. A 12-bit counter has a maximum duration of T_(cntr)=4096·T_(θ). Inthe earlier case, where the clock period T_(θ)=107 μsec, the maximumduration is 438 msec corresponding to a synthesized waveform having afrequency n lower than f_(synth)≦2.28 Hz. As shown in FIG. 15E, thisapproach entails running the counter to its full count. As such theT_(sync) period is set equal to the maximum clock count. By utilizingthe microcontroller to rewrite and retrigger the counter many times, anylow frequency can be produced. In the example shown in FIG. 15F, Clk 254along with Sync pulse 253, retriggers the counter three times resultingin low frequency waveform 256 having an on time of 1.5T=657 msec, aperiod of 1,314 msec, and a corresponding digital pulse frequency 0.76Hz. By combining firmware or software control in the microcontrollerwith hardware counters in the LED driver ICs, any low or extremely lowwavelength frequency can be generated, even at frequencies my lower thanthat produced by the full count of the counters used within the LEDdriver ICs.

In conclusion, waveform synthesis for LED phototherapy using LED driverICs combined with microcontroller originally intended exclusively for TVbacklighting offers a flexible means by which to synthesize varyingfrequencies and patterns needed for photoexcitation and sequencing ofmultiple wavelength LEDs. Unlike in HDTVs, where the duty factor variesand the Vsync period remains constant, in the disclosed phototherapydevice, LED on-time t_(on), the period T_(sync) of the Sync pulse andthe frequency of Clock θ, both generated by microcontroller 209, canvary dynamically, changing the clock rates either continuously or eachtime a new Sync pulse occurs. Implementing an LED drive system with avarying time base and time varying Sync pulses is completely contrary tomandating the use of fixed rate Vsync pulse rates in HDTVs conforming tointernational video broadcast standards and complying with governmentcommunication regulations. So while phototherapy can employ dynamicclock methods (similar to computer cores), video systems cannot.

Programmable Brightness Control

Like backlighting in HDTVs, the LEDs in a phototherapy LED pad likewiserequire brightness control. While TV backlighting systems perform dutyfactor based PWM brightness control using a fixed frequency coming fromthe TV's vertical sync signal, and utilize the full 12-bit counter forprecision dimming and phase delay control, LED drive in phototherapy isnot based on fixed frequency dimming, but instead must synthesizewaveforms having both programmable frequency and dimming control too.

Unlike in TV backlighting, the duty factor is not the value of clockpulses residing in the individual channel's t_(on) register divided bythe full count of 4096, but instead must be calculated for eachsynthesized frequency. This task is performed algorithmically withinmicrocontroller 209 interfaced to the LED driver IC 207 through SPI bus213. The algorithm for these calculations is described later in thisdisclosure.

FIG. 17A illustrates examples of fixed frequency PWM dimming.In theexamples shown, the clock period is a fixed value of nT_(θ) (shown forconvenience as n=8), but in practice the count “n” implemented inmicrocontroller 209 may be much larger. In waveform 281, an array ofLEDs having wavelength λ is illuminated 6 out of 8 clock pulses having asynthesized duty factor and corresponding PWM controlled brightness ofD=6/8=75%. The frequency of the synthesized waveform fsynth=1/nT_(θ) isprogrammed to a prescribed value using the techniques described in theprior section. At time t1, the microprocessor changes the value of tonfrom 8 to 2 pulses resulting in a change to the synthesized duty factorto D=2/8=25%.

In the example waveform 282, at time t₁ both the duty factor controlledPWM brightness and the LED wavelengths are changed. Prior to thetransition an array of LEDs having wavelengths λ₂ are illuminated withan on-time of 4 pulses for a resulting duty factor and PWM brightness ofD=4/8=50%. After time t₁, the LED array changed to LEDs having awavelength λ₃ and a PWM controlled brightness of D=6/8=75%.

In waveform 285 of FIG. 17B, the PWM brightness, synthesizedfrequencies, and LED wavelengths are all changing. Prior to time t₁, anarray of LEDs having wavelength λ₂ is illuminated with an on-time t_(on)(by example with t_(on)=6 pulses) and a synthesized periodT_(synth1)=nT_(θ) (by example where n=8 pulses) corresponding to a dutyfactor D=6/8=75%. At time t₁, the same array of LEDs with wavelength λ₂changes to t_(on)=4 pulses corresponding to a duty factor of 50%. Attime t₂, the array of LEDs with wavelength λ₂ is shut off and an arrayof LEDs with wavelength λ₃ is turned on with a new on-time t_(on) (byexample where t_(on)=1 pulse) and a new period T_(synth2)=mT_(θ) (byexample where n=4 pulses). The result is a new synthesized frequencytwice that of the prior frequency, i.e. where f_(synth2)=2f_(synth1) andwhere D=25%.

In the above description, the duty factor control setting PWM brightnesslevel of an array of LEDs is achieved by adjusting the on time t_(on)for any given synthesized frequency f_(synth) and corresponding periodT_(synth), as given by the relationD=t _(on) /T _(synth) =t _(on) ·f _(synth)

In practice, one fixed frequency waveform is synthesized for an extendedduration Δt, typically from minutes to tens of minutes.

In an alternate embodiment, the synthesized periodT_(synth)=t_(on)+t_(off) varies for each and every pulse. The result isa continually varying frequency spectrum. Examples of algorithms forsuch variable frequency operation include constant on-time variablefrequency operation, constant off-time variable frequency operation,constant duty factor variable frequency operation, and swept frequencyoperation.

In the case of constant on-time variable frequency synthesis shown inFIG. 17C, a desired spectrum of frequencies is generated undermicrocontroller control having a fixed and constant on-time t_(on) and aconstantly varying off time t_(off), duty factor D, period T_(synth) andwith a corresponding frequency f_(synth) as given by the relationT _(synth)=1/f _(synth) =t _(on(constant)) +t _(off(variable))where t_(on(constant)) is set to a fixed interval (having by exampleduration t_(on(constant))=2 pulses as shown), and having a valuet_(off(variable)) constantly being varied. As t_(off) varies so too doesT_(synth) and duty factor D=t_(on)/(t_(on)+t_(off)). A series of pulseswith off periods ranging from 1 to 7 clock intervals is shown and theresulting equivalent synthesized frequency and duty factor as summarizedin Table 2. For illustrative purposes, the synthesized frequencyf_(synth) depends also depends on the frequency of Clk θ, illustratedfor fixed frequency values of 9,346 Hz (with corresponding clock periodT_(θ)=107 μs) and 935 Hz (with corresponding clock period T_(θ)=1070μs).

TABLE 2 Constant on-time variable frequency method Pulse Wavelengtht_(on) t_(off) T_(synth) D = f_(synth) (Hz) f_(synth) (Hz) # LED Clk θClk θ Clk θ (μs) t_(on)/T_(synth) T_(θ) = 9,346 Hz T_(θ) = 935 Hz 1 λ₂ 22 4 (428) 50 2,336 234 2 λ₂ 2 1 3 (321) 67 3,115 312 3 λ₂ 2 4 6 (642) 331,558 156 4 λ₂ 2 7 9 (963) 22 1,038 104 5 λ₃ 2 3 5 (535) 40 1,869 187 6λ₃ 2 0 2 (214) 100 4,673 467 7 λ₃ 2 2 4 (428) 50 2,336 234

As shown, the 6^(th) pulse is programmed for 100% duty factor, i.e.t_(off)=0. The ability to achieve a zero off time pulse depends on theLED driver IC and the frequency of operation. In some cases, the LEDswill remain on for the entire period T_(synth) but may thereafter try toturn off. Due to the finite transition time required to turn the currentsource off and back on a small off interval or “glitch”288 unrelated tothe clock period T_(θ) may result. The impact of this glitch is toslightly shorten the on time of the subsequent pulse, meaning the dutyfactor of the 7^(th) pulse will be slightly reduced from the 50% shownin the table. If however, the glitch does not occur, the 6^(th) pulsewill merge with the on portion of the 7^(th) pulse, resulting in a4-pulse on-time as a 2-pulse off-time. The hybrid mix of the 6^(th) and7^(th) pulses results in a 6-clock pulse period with a duty factorD=4/6=66%.

Constant off-time LED drive algorithms are similar to the above tableexcept that the data in the t_(on) and t_(off) columns are switched. InLED drive, the result of constant on time and constant off-time variablefrequency LED drive algorithms is that the synthesized photoexcitationfrequency f_(synth) and the PWM brightness of the LED arrays areproportional with a fixed ratio. In constant duty factor variablefrequency drive, the on time scales with frequency to maintain aconstant duty factor so that the frequency varies but the brightnessdoesn't. In general, constant brightness is more useful in LED drivethan continuously varying the brightness.

Another possible variable frequency algorithm is swept frequencyoperation, where the frequency increases or decreases monotonicallyduring operation, e.g. starting at 10 kHz and sweeping down to 10 Hzover an interval of minutes to tens of minutes, or alternativelystarting at 5 Hz and sweeping up to 5,000 Hz over an interval of minutesto tens of minutes. Again holding the brightness constant (adjusting theon-time to maintain a fixed duty factor and PWM brightness) is generallypreferable to varying the LED brightness.

Finally LED current using PWM brightness and duty factor control can beused to blend LEDs of different wavelengths controlling their mix, i.e.their “blend” by their relative brightness. For example, in FIG. 18, anarray of LEDs having a wavelength λ₂ is illuminated to a PWM-controlledbrightness 28% that of an array of LEDs having a wavelength λ₁. In theexample of concurrently illuminated waveforms 289, prior to time t₁, theLED array having wavelength λ₂ are driven with a PWM duty factor of 50%,while the array of LEDs with wavelength λ₂ are driven at a PWMbrightness of 14%, i.e. at a brightness 28% of the concurrentlyilluminated LEDs. After time t₁, the LED array having wavelength λ₁ aredriven with a PWM duty factor of 70%, while the array of LEDs withwavelength λ₂ are driven at a PWM brightness of 20%. Despite changingthe overall LED brightness, the ratio of the brightness of the λ₂wavelength LEDs to that of the λ₁ wavelength LEDs remains at 28%.

LED Current Control

Although LED current control can be used to control LED brightness, thequantum efficiency of LEDs varies with current producing more heat andless photons per power consumed at higher currents. For that and forsafety reasons the current of LEDs should in general be biased tomoderate levels, e.g. 20 to 30 mA each, depending on the LED'sconstruction. Another reason to employ LEDs running at more moderatecurrents is that high-current high-brightness LEDs are substantiallymore expensive in the market and have fewer suppliers supporting theirmanufacture. In phototherapy applications, concentrating high-brightnesslight into a small area makes it more difficult to obtain a uniformlight intensity over a large area such as the entirety of a LED pad thanusing a higher density of LEDs with lower brightness levels.

Even though dynamic brightness control may be achieved by PWM dimmingrather than adjusting LED current, LED current remains important inobtaining good brightness uniformity across an LED pad. In FIG. 12 (withone channel shown by example shown in inset 300 of FIG. 19) each channelcomprises a precision gate bias and control circuit 215 a through 215 ncontrolling a corresponding current sink MOSFET 216 a through 216 n andLED string 205 a through 205 n. The current passing through each MOSFETis monitored by the precision gate bias circuit and compared to areference current αI_(ref). Any error between the reference current anda ratio equivalent of the measured LED current results in a dynamicadjustment of gate bias higher or lower in voltage until the twocurrents match. Because the LED current is mirrored and trimmed foraccuracy using a low voltage current sink or a operational amplifier,the actual reference current need only comprise a fraction of the LEDs'currents I_(LEDa) through I_(LEDn) but for simplicity's sake we willtreat the reference current as though it has the same magnitude, i.e.where I_(LED)(max)=I_(ref).

This maximum LED current in each channel of LED driver IC 207 is set bythe value of I_(ref), and in most cases set only once for eachmultichannel LED driver IC by a single external precision resistorR_(set) and a common precision voltage reference V_(ref). To guaranteesuperior channel-to-channel matching, the precision voltage V_(ref) isshared by all the channels (and preferably by all LED driver ICs). Themaximum LED current is set by the resistor value when the digitalmultiplier α=100% (set by the digital data register I_(LED) through theSPI bus) and is given by the relationI _(LED)(max)=αI_(ref)whereI _(ref) =k(V _(ref) /R _(set))

For safety, this value can be set to an I_(LED)(max) current value forthe maximum brightness that conforms to international and governmentalhealth and safety standards. The maximum value occurs whenever theI_(LED) register 301 is set to a value whereby where α=100%. Therelationship between the digital register-code loaded in I_(LED) dataregister 301 and the analog value αI_(ref) output from D/A converter 302is illustrated in the graph of FIG. 19. Assuming D/A converter 302comprises an 8-bit digital to-analog converter circuit, then the channelcurrent αI_(ref) can be controlled into 256 levels from 0 mA (off) to100% ·I_(ref) in 0.39% steps.

In digital programming a 8-bit or 1-Byte word can be represented by twohexadecimal characters ranging from a hexadecimal code 00 representingthe 1^(st) step 305 has a value αI_(ref)=0 while a hexadecimal code FFrepresenting the 255^(th) step 306 has a value αI_(ref)=100% ·I_(ref).The following equation converts a hexadecimal number into its decimalequivalent:Decimal=(Hex₁·16+Hex₀)

So to convert hexadecimal FF Into its decimal representation (where F isequal to 15) is given by (15·16)+15=255 or 100%. Although anymathematical transfer function can be represented, for simplicity's sakelet us assume a linear relation, I_(LEDn)=[(Hex₁·16+Hex₀)/255]·I_(ref)

where the code for hexadecimal 80 or decimal step 8·15+0=128 representsthe value (128/255)·I_(ref) or roughly 50% of the peak current.

Intentionally, most current step increments have been hidden (they liein the gap 307) from the graph of FIG. 19 for clarity's sake. For thosecurrent step increments that are shown, each step includes the constantvalue of current 303 and an analog representation of the light waveoutput 304 from the LEDs (similar to the composite signal representationdescribed previously in FIG. 10C). Notice that as the current increasesthe magnitude of the sine wave representing the light output increasesin amplitude.

In another embodiment of this invention, programmable registers withinmicrocontroller-209 limit the current αI_(ref) set by A/D converter 302to preprogrammed maximum values by restricting the allowed I_(LED)register code by login privilege or security code. In the phototherapyapparatus disclosed herein, user login or security codes establishedduring manufacturing or setup, restrict the machine's high poweroperating modes to skilled physicians or approved technicians. Forexample, while a clinician may be restricted to operating the machine upto a maximum brightness of 50% or Hex 80, a practicing physician may beauthorized to operate the machine up to an I_(LED) register code of hexE4 or in decimal to (14·16+4)/255=89%.

This means a physician can operate the apparatus to a setting 89% of themaximum brightness while other users are limited to 50% of the maximumbrightness. In the worst case, should the machine malfunction, themaximum possible brightness set by the value of resistor permanentlysoldered into the circuit during manufacturing is still limited to alevel defined as “safe” from regulatory agencies.

Aside from enabling security and safety features the other benefit ofprogrammable I_(LED) register 301 is to compensate for non-uniformitiesin LED brightness. Inconsistent brightness in LEDs results frommanufacturing variations, from crystalline defects in LEDs, by mixingdifferent manufacturer's devices into the same phototherapy apparatus,or by simultaneously driving LED strings having different wavelengths.FIG. 20 illustrates the optical output power of an LED versus itscurrent, here represented by the corresponding values of α inpercentage, and by the digital and hexadecimal code in I_(LED) dataregister.

As shown three LEDs 310, 311, and 312 operating at a nominal current of0.5·I_(ref) as programmed by hex code 80 (128 decimal equivalent) in theI_(LED) data register exhibit three optical power outs P₂, P₁ and P₃respectively. These variations may occur as a result of naturalstochastic variability in LED manufacture or because the LED stringsrepresent arrays of LEDs having differing wavelengths λ. In the eventthat the LEDs have different wavelengths, the channel driver's CSFBcircuit compensates for variation in the LEDs' forward voltages. Thedifference in brightness is therefore not related to forward voltage butsimply the current dependence of LED brightness.

Regardless of the mechanism, if the LED array is intended to exhibit auniform power output P₁ across the LED pad's surface, LEDs 310 and 312must be driven under different current conditions to achieve the sameoptical power output as LED 311. Since the on-time and clock periods areemployed algorithmically to determine an LED's PWM controlled brightnessD and synthesized frequency f_(synth1), it is preferable not tocomplicate the PWM control function to compensate for mismatched LEDbrightness. Instead, the mismatch can be compensated for using theI_(LED) setting once during manufacture and can be ignored thereafter.If for example LED 310 has its current changed from the nominal value ofhex 80 to hex 84 (decimal 132), the LED's current increases to0.52·I_(ref) and as a result, the LED optical output increases from P₂to P₁ as desired. Similarly if LED 312 has its current changed from thenominal value of hex 80 to hex 7E (decimal 126), the LED's currentdecreases to 0.49·I_(ref) and as a result, the LED optical outputdecreases from P₃ to P₁ as desired.

By storing the hexadecimal values of I_(LED) for LEDs 310, 311, and 312permanently in nonvolatile memory within the microcontroller 209,broadcasting the LED current settings (hex 84, hex 80, and hex 7Erespectively) over the SPI bus and loading them into their correspondingI_(LED) registers within the channel drivers 207 a through 207 n atstartup as shown by the I_(LED) data registers 301 d through 301 h inFIG. 21, dissimilar LEDs can be biased to the same brightness despitetheir manufacturing differences. The I_(LED) values stored in themicrocontroller then serve as a type of compensation or correction tablefor LED brightness.

Phase Delay

As shown previously, waveform synthesis combining microcontroller 209with LED driver IC 207 is capable of driving arrays of varyingwavelength LEDs in flexible sequences, user defined photoexcitationfrequencies f_(synth), and varying levels of PWM brightness. It was alsoshown while the phase delay Φ can be employed in the waveform synthesisprocess, the judicious use of t_(on) along with Clk θ and Sync signalscan produce all the desired waveforms needed for a phototherapyapparatus without using phase delay Φ for such tasks. As such, phasedelay Φ remains available for implementing other important features.

Once such notable feature is shown in the graph of FIG. 22 where thecurrent demand drawn by the multiple channels of an LED driver (seemultichannel LED driver example in inset 320) is plotted against elapsedtime during startup of the system. In curve 324, a phototherapyapparatus with no channel delay is started at time t_(a) comprising anarray of LEDs of a particular wavelength all turned on at once andconducting (while other wavelength LEDs remain off). The result is acurrent spike 323 which can reach peak currents more than double ortriple the normal steady current consumption 322 of the system.

If instead of turning all the channels on at one time the LED array isturned on with a programmable phase delay, the channels commenceconducting in a sequence so they don't all try to conduct at once,greatly diminishing the turn on current spike. For example, by onlyturning on one string of LEDs at time t_(a) with no phase delay (i.e.where phase delay Φ=000 hex), the inrush current is changed from curve323 with a peak current of 300 mA to that of curve 320 having a peakinrush current of 40 mA, improving the inrush current by better than afactor of 7×.

After the inrush the current stabilizes to current 321 representing thesteady state conduction of one LED string, a second string of LEDs withphase delay Φ=008 hex then turns on after 8 pulses at time t_(d)followed by a third string with phase delay Φ=010 hex turning on afteranother 8 pulses at time t_(g), followed in succession by a fourth,fifth, and sixth string with phase delays Φ=018 hex, 020 hex, and 028hex, each turning on in 8 pulse increments at times t_(l), t_(m), andt_(p) respectively. As a result the peak current only slightly exceedsthe steady state LED current 322 or 120 mA. As a result, the inrushcurrent is held below half of the spike current 323 conducted duringturn on without the phase delay feature.

Microcontroller and Waveform Synthesis Algorithm

FIG. 23A represents an exemplary phototherapy waveform synthesisalgorithm of the disclosed method and apparatus. The algorithm is notintended to suggest a specific sequence or therapy but rather to combineby way of example many of the previously defined operational elementsand control variables.

In the example, only a few variables remain common system wide,particularly the current reference I_(ref), the period of sync pulsesT_(sync), and the frequency f_(θ) the clock signal Clk θ used forcounting in the various channel timers. While these parameters areglobal, meaning shared and common to the different operations, they aredynamic and can vary over time. As shown, T_(sync) previously variescontinuously during any variable frequency waveform synthesis and insome cases so does clock frequency f_(θ).

All the other variables are defined specifically for each operation,namely the PWM brightness control duty factor D, the frequency f_(synth)of the synthesized waveform, the phase delay Φ of each conductingchannel during turn on, and the channel current αI_(ref). The variablesD and f_(synth) are not actually control variables, per se, but thesynthesized result of the combined control of t_(on) for a specificchannel or array of LEDs, along with the global variables T_(sync), andpossibly f_(θ).

In the example of phototherapy waveform synthesis algorithm 330,operation 171 a comprises generation of synthesized frequency f_(syntha)for duration Δt_(a) having PWM brightness D_(a) conducting currentα_(a)I_(ref) in LEDs 120 having a wavelengths in the band λ₂±Δλ₂.Operation 171 a is then immediately followed by operation 171 bcomprising synthesized frequency f_(synthb) for duration Δt_(b) havingPWM brightness D_(b) conducting current α_(b)I_(ref) in LEDs 120 havingthe same band of wavelengths λ₂±Δλ₂. The waveform synthesized fromoperation 171 b is blended for duration Δt_(g) with LEDs 110 ofwavelengths λ₁±Δλ₁ having a PWM brightness D_(g) and biased at currentα_(b)I_(ref).

Thereafter operation 171 c comprises generation of synthesized frequencyf_(synthc) for duration Δt_(c) having PWM brightness D_(c) conductingcurrent α_(x)I_(ref) in LEDs having wavelengths in the band λ₃±Δλ₃.Alternatively, in flow 173, operation 171 c can be skipped altogether,or in flow 172 laser light 135 having a spectral band λ₃±δλ₃ isilluminated for a duration Δt_(f) with PWM brightness D_(f), phase delayφ_(f) and biased at current α_(f)I_(ref). Thereafter operation 171 dcomprises a delay Δt_(d) where no LED or laser is illuminated followedby operation 171 e, comprising generation of synthesized frequencyf_(synthe) for duration Δt_(e) having PWM brightness D_(e) conductingcurrent α_(e)I_(ref) in LEDs 110 having a wavelengths in the bandλ₁±Δλ₁. Alternatively (not shown), a separate array of the samewavelength LEDs 110 can be “harmonized” with those in operation 171 ebeing illuminated under the same driving conditions except having asynthesized frequency f_(synthg) different than and preferably an evenharmonic of synthesized frequency f_(synthe). The entire process canthen be repeated (flow 174) in totality or in part as desired.

The result of phototherapy waveform synthesis algorithm 330 is shown inthe timing diagrams of FIG. 23B comprising the illumination of arrays ofLEDs of wavelengths λ₁, λ₂, and λ₃ in diagrams 251, 252 and 253, of thecombined output λ_(out) mixing of varying wavelengths 253, and the totalpower output P_(λout) of the varying LED wavelengths 254, all referencedto clock Clk θ 180 as a common time base. For simplicity, the LEDoutputs of only the main sequence in algorithm 330, comprisingoperations 171 a, 171 b, 171 c, 171 d, 171 e, and 171 g is shown.

During interval Δt_(a) operation 171 a results in a waveform having arepeated period 1/f_(syntha) and a PWM brightness approximatelyD=12/18=67%. While the interval shows only two cycles of the synthesizedwaveform, it should be understood that Δt_(a) is minutes or tens ofminutes in duration, while f_(syntha) is milliseconds or tens ofmilliseconds in duration and cannot accurately be represented on thesame time scale. Likewise it should be understood that duration Δt_(b),Δt_(c), Δt_(d), and Δt_(e) also comprise intervals of minutes to tens ofminutes in duration and the synthesized waveforms have frequenciesorders of magnitude faster.

Continuing with FIG. 23B, in interval Δt_(b) operation 171 b results ina waveform having a repeated period 1/f_(synthb) and a PWM brightnessapproximately D =4/7=57%. In Interval Δt_(c) operation 171 c results ina waveform having a repeated period 1/f_(synthc) and a PWM brightnessapproximately D=6/12=50%. In interval Δt_(e) operation 171 e results ina waveform having a repeated period 1/f_(synthe) and a PWM brightnessapproximately D=16/19=85%. If f_(θ)=935 Hz, then T_(θ)=1.07 ms andf_(syntha)=1/((1.07 ms)·18)=52 Hz. Similarly f_(synthb)=134 Hz,f_(synthc)=78 Hz, and f_(synthe)=49 Hz. Alternatively if a clock tentimes faster is employed, i.e. where f_(θ)=9,356 Hz, then all thesynthesized frequencies will likewise be ten times higher.

It should also be reiterated that the sine waves in FIG. 23B representthe optical output of the LEDs and are also not represented on the timescale, since the frequencies of infrared and visible light are manyorders of magnitude higher than that of the synthesized frequencies.

FIG. 24 illustrates a block diagram representation of microcontrollerfunctions in phototherapy system and apparatus. As shown, LED drive andcontrol 206 comprises microcontroller 209 with keypad 211 and touchscreen 212, SMPS 208 and one or more LED driver ICs 207 driving variousarrays of LEDs 205 a comprising LEDs or laser diodes having any numberof wavelengths λ.

Microcontroller 209 contains hardware, memory, firmware and softwareinterface and control elements, including

-   -   pattern library 210 a comprising data and non-volatile memory        containing any number of photoexcitation algorithms,    -   SPI bus interface physical interface 210 b with hardware and        firmware based clocking and protocol management (including high        speed physical bus and 10 MHz SPI-bus clock SCK used for        clocking SPI data),    -   LED setting register 210 c comprising memory and data containing        preset and reconfigurable LED bias and drive settings for each        wavelength of LED (including sequence duration Δt, synthesized        frequency f_(synth), PWM brightness control by duty factor D,        turn-on phase delay φ, and current multiplier α₁),    -   fault management unit 210 d comprising firmware and hardware        including fault detection and recovery algorithms for a variety        of fault conditions (such as shorted LED detect, open LED        detect, and over-temperature detection).    -   clock and timing interface 210 e comprising hardware, firmware        and software for dynamically generating global system timing        clocks (including Sync and Clk θ),    -   program command and control unit 210 f comprising internal data        busses, data stacks, program counters, pointers, data        accumulators, registers, firmware and software needed for        instructing the arithmetic logic unit (ALU), counters, shift        registers, and data storage in microcontroller 209 how to        algorithmically synthesize waveforms,    -   software algorithm based waveform synthesis 210 g comprising        program software and core ALU used to algorithmically synthesize        waveforms and to generate control signals for LED driver ICs 207        (including dynamically varying sync pulse Sync having period        T_(syncx), dynamically varying counter Clk θ pulses having        period T_(θx), dynamically determining the LED on-time t_(onx)        for each and every channel of LEDs, dynamically determining the        LED phase delay during turn-on Φ_(x) for each and every channel        of LEDs, and dynamically setting the digital register data        I_(LEDx) for each and every channel of LEDs),    -   user interface 210 h comprising a physical interface with        firmware and software for decoding keypads, driving LCD        displays, interpreting touch screen instructions, communicating        user selections to program and control 210 f (used to select        algorithms and overwrite preset operating parameters), as well        as to perform user identification and enforce login or used ID        based security and privileges,    -   analog interface 210 i comprising hardware and firmware        including data analog-to-digital (A/D) and digital-to-analog        (D/A) converters for connecting to sensors and analog        biofeedback information or for outputting analog control signals        (such as Vref used by LED driver ICs 207), and    -   digital interface 210 j for connecting to digital inputs from        sensors and other digital biofeedback information (including        digital data handshaking with external devices and peripherals)        and alternatively for interfacing to digital communication        busses such as Ethernet, USB, IEEE1394, PC Express cards, and        Thunderbolt, or to wireless data communication such as        Bluetooth, WiFi, 3G, or 4G/LTE.

As shown, microcontroller 209 sends its instructions to LED driver ICs207 through a high-speed digital bus, shown here as SPI bus 213 (withhigh-speed data handshaking managed by SPI serial clock SCK). Analoginterface 210 also generates a precision voltage reference V_(ref) usedby analog control and sensing circuit 219 within each LED driver IC 207to generate the precision reference current I_(ref). Alternatively,V_(ref) can be generated using discrete components. Clock lines 223 aand 223 b comprising counter clock Clk θ and Sync pulse signals areconnected to counters 221 a through 221 n in LED driver IC 207.

Within LED driver IC 207 control and interface circuit 214 includes asingle SPI bus interface 214, one per driver IC and an internal digitalbus 222 communicating with decoders 227 a through 227 n (one decoder perchannel). The decoded data is transferred to corresponding registers 224a through 224 n, 225 a through 225 n, and 226 a through 226 n,respectively for t_(on),Φ , and I_(LED) data, respectively. Upon thenext Sync pulse the t_(on), and Φ data is loaded into counters 227 athrough 227 n and I_(LED) data is loaded into D/A converters 228 athrough 228 n, controlling precision gate bias and control circuits 215a through 215 n. As a result, the currents flowing through MOSFETs 216 athrough 216 n and LED strings 205 a through 205 n are individuallycontrolled by microcontroller 209.

FIG. 25 illustrates a flow chart of the microcontroller 209's setup andoperation in the disclosed phototherapy apparatus, comprising steps 300through 304. During manufacturing 300, the system is configured for themaximum possible LED current defined by I_(ref) and set by trimmingV_(ref) to a precise value and selecting a value for R_(set)corresponding to the maximum allowable current (i.e. where the I_(LED)register is set to FF so that α=100%) for a particular model andgeographic sales region or country. The nominal value operating currentis then determined by scaling this maximum current to a lower numberusing the I_(LED) data register and storing this value in a defaultregister. Likewise, during initialization of a new unit, defaultalgorithms are loaded into pattern library 210 a, and default values forLED bias and operating conditions are loaded into LED setting register210 c for each type and wavelength of LED. During initialization, thecorresponding LED pad configuration including the number of LED channelsn and the number of LEDs in series m is also loaded into defaultregisters. During final electrical test, the LED pad may optionally beset into calibration mode where all the LEDs of a given wavelength LEDare operated at full brightness and the default values of I_(LED)adjusted to achieve the best uniformity of brightness. This process isrepeated and stored in a default register for I_(LED). All defaultregisters are stored in nonvolatile memory as described previously.

In an alternative embodiment of this invention, the apparatus is able todetect the attached LED pad and automatically configure the unit for thepad's particular configuration including its total number of LEDs, thenumber of channels, the number m of series-connected LEDs in an LEDstring, and the wavelengths of the LEDs used in each channel.

Before using the phototherapy apparatus, a physician or clinician firstperforms user setup 301 involving a login or security check to determinethe user's privileges. Upon confirmation of the login ID and password,the apparatus loads programs and settings previously stored by the userinto the menu selection. A successful login also enables privilegesestablished by the device owner for that particular user. Suchprivileges may include the ability to change default settings, to createnew recipes and algorithms, and for those with the appropriatecredentials to operate the devices at a higher than normally allowedpower level. For example, a physician may be authorized to drive LEDs atcurrents of 30 mA, while all other users are limited to current 20 mAand below. In the absence of a login, the unit can either be preventedfrom operation or allowed to operate in a restricted manner, e.g.limited to certain generic algorithms and LED settings.

To commence operation, the user first selects a pattern, i.e. apreprogrammed algorithm closest to the desired treatment. The algorithmsstored in pattern library 210 a specify various sequences for drivingLEDs, including the LED wavelengths λ and corresponding photoexcitationfrequencies f_(synth) for each step in the sequence. When selected fromthe pattern library, the algorithm is copied into volatile memory,specifically by reading the contents in the selected non-volatile memoryand copying it into SRAM. The chosen algorithm automatically selectsdefault conditions for driving each wavelength of LED for each step inthe algorithm, including duration Δt, synthesized frequency f_(synth),PWM brightness (set by duty factor D), turn-on phase delay Φ, and theLED current multiplier α (set by the I_(LED) calibration curve). Onceselected, these LED conditions stored in “LED setting register” 210 care copied into RAM from non-volatile memory.

Also during user setup 301, the default conditions for how the apparatusdetects and deals with operating faults are copied from non-volatile“fault recovery” register into RAM. Operating faults includemalfunctions in LED pads or cabling leading to the detection of “open”or “shorted” LEDs, or the detection of over-temperature conditionsoccurring in any LED pad or in any LED driver IC. Choices available whena fault condition occurs include shutting off the entire systemimmediately, disabling the malfunctioning channel, adjusting the biasconditions and confirming if the fault disappears, operating the unitwith the fault by backing off on the drive currents, or ignoring thefault until a subsequent fault is detected.

In the case of over-temperature detection, a warning sent from an LEDdriver IC informs the microcontroller that the IC is overheating. In oneembodiment, the microcontroller then identifies any channel with ashorted LED and either shuts it off or reduces the current in thatchannel, checking again to confirm that the fault has been cured orshutting it down. A secondary thermal protection circuit insures thedevice is shut off before a dangerous temperature occurs, independent ofmicrocontroller instructions.

User setup 301 facilitates control of the phototherapy apparatus inaccordance with a user's privileges. By copying the selected programalgorithm, LED settings, and fault recovery settings into RAM, anauthorized user can change recipes and LED settings via keypad 212 ortouchscreen 211 without the risk of accidentally modifying the unit'sdefault settings stored in non-volatile memory.

While the disclosed invention synthesizes photoexcitation frequenciesf_(synth) using square wave pulses, other waveforms such as sawtooth,triangular, and sine wave synthesis are also possible.

After the conditions are chosen, the operation 302 in FIG. 25illustrates that a number of variables must then be calculated beforeoperation commences. Calculated variables most importantly include theperiod T_(sync) of the Sync pulse and the on time t_(on) for everychannel, variables shown to change with virtually every step in waveformsynthesis. These calculations depend on the frequency of Clk θ sincethis clock represents the time basis for the counters used in frequencysynthesis, brightness control and phase delay.

In one case, the selection of the clock period T_(θ) of Clk θ is set asfixed multiple of T_(sync) either equal to the maximum count of thecounter or alternatively to some lesser ratio. For example if a 12-bitcounter is employed, Clk θ may operate at a frequency 4096 times fasterthan the Sync pulse, or if higher speed is preferred over precision,then Clk θ may operate at a frequency 1024 times higher than the Syncpulse. In an alternative embodiment, Clk θ is free-running and the Syncpulse occurring whenever it is required to update data withoutinfluencing Clk θ. For the sake of discussion, we assume a fixed T_(θ)and a dynamically varying period for T_(sync).

Once the frequency f_(synth) is selected for a particular LED wavelengthand a given step in the sequence, the microcontroller calculates theappropriate period T_(synth) corresponding to the selected frequencywhere T_(synth)=1/f_(synth)=n_(synth)T_(θ). The Sync pulse is thengenerated at the period of the synthesized waveform, i.e.T_(sync)≡T_(synth). If, however, more than one frequency is beingsynthesized simultaneously the highest frequency, i.e. the shortestvalue of T_(synth) should be used to determine the Sync pulse.

Each conducting channel must repeat its cyclic count corresponding itssynthesized frequency. Rearranging the relation in terms of the numberof Clk θ clock pulses n_(synth) results inn _(synth) =T _(synth) /T _(θ)=1/(T _(θ) ·f _(synth))

This means that a specific channel must restart its sequence veryn_(synth) pulses. If only frequency is being synthesized, this restartoccurs once for every Sync pulse. If the fastest frequency is beingsynthesized on a given channel, then for that channel the restart alsooccurs once for every Sync pulse. If however, a frequency is beingsynthesized in a phototherapy system generating multiple frequencies,then multiple Sync pulses may occur before the specific channel repeatsits cycle. In such cases the microcontroller must calculate the pulsesremaining and exhaust that count before restarting the cycle and againturning on the channel, i.e. setting t_(on)>0.

The desired brightness (specified by the algorithm as duty factor D) isused to calculate the on-time t_(on) for each channel also representedby the number of pulses, where byt _(on) =D·n _(synth)

This calculation is performed for every channel. So for each channel,the microcontroller calculates an on time described by the number ofclock pulses t_(on) and a period T_(synth) specified by a number ofclock pulses n_(synth). For each Clk θ pulse the value of n_(synth) andt_(on) within the microcontroller waveform synthesis calculation aredecremented by one pulse, having a current value represented by thevariables n′_(synth) and t′_(on).

Provided that a Sync pulse does not occur first, when the t_(on) countreaches zero, the counter in the channel driver will shut off thatchannel's LED string. Meanwhile the microcontroller will continue tocount down the balance of pulses remaining in the n_(synth) register andotherwise take no action to update the registers in the LED driver ICs.Also, provided that during this interval a Sync pulse does not occurfirst, when the n_(synth) count for the channel finally reaches zero,the microcontroller generates a Sync pulse, and the channel is reloadedwith the original value for t_(on) turning the off LEDs in the channelback on and restarting the counter. Concurrently within themicrocontroller program the full value for n_(synth) is reloaded and thecount down starts anew.

If a Sync pulse, however, occurs before either the t_(on) counter or then_(synth) counter reach zero, then the current balance of t′_(on) isrewritten to the counter in the channel driver, thereby keeping the LEDchannel on and restarting the counter with the new (smaller) value ofremaining on time, while the microcontroller continues to decrement then′_(synth) counter unabated until it reaches zero.

Alternatively, should a Sync pulse occur after a channel has turned off(i.e. after the t_(on) counter has counted down to zero), but before thesynthesized period has been completed where the n_(synth) counter hasnot yet reached zero, then when the Sync pulse occurs the channelon-time must be rewritten to the registers in the channel driver withthe value t_(on)=0 to maintain the channel in its off state while themicrocontroller continues to decrement the n′_(synth) counter unabateduntil it reaches zero.

In summary, the number of clock pulses n_(synth) represents the countneeded to synthesize a desired frequency as specified by a givenalgorithm and LED settings selected from pattern library 210 a and LEDsetting register 210 c whether modified or unaltered by a user. Wheneverthe present value of n′_(synth) counts down to zero on any channel inthe system, the microcontroller automatically sends a Sync pulse. Inresponse to the Sync pulse, the channel that caused the Sync pulsereloads its t_(on) register, turns on its LED string anew, and startscounting it's n_(synth) count all over again. In response to the Syncpulse, any channel that is still on must reload its present remainingt′_(on) balance into the t_(on) register of the channel driver (keepingthe LED string on) and restarting the count down, while continuing todecrement it's n′_(synth) count without any changes. Alternatively inresponse to the Sync pulse, any channel that already off must reload itst_(on) register with zero (thereby keeping the LED off), whilecontinuing to decrement it's n′_(synth) count without any changes.

While the algorithm is described above using counters, since the timesand clock rates are specified a priori, the actual clock pulse when theSync pulse is to be generated can be calculated in advance, stored in aregister and compared to the value in the counter generating theT_(sync) pulse from the Clk θ clock. When the defined conditions occur,the Sync pulse is generated and the appropriate data is loaded into theLED driver IC's data registers.

Referring again to operation 302 “calculate drive parameters”, the valueof the total duration Δt specified in clock pulses is simply the realtime duration (in minutes) divided by the clock period T_(θ). The valueof current I_(LED) is directly copied from the calibration table. If adifferent value is desired, the correction for the calibration should beadded or subtracted linearly to the desired number to maintain anaccurate brightness.

For phase delay, unless manually overwritten the clock delay Φ=zspecified is added incrementally to each channel so that the delaylinearly propagates (as shown in FIG. 22) whereby for each channel

-   -   Φ₁=0    -   Φ₂=z    -   Φ₃=2z    -   Φ₄=3z    -   Φ_(n)=(n−1)z

To engage treatment 303, the user has an option to scale the treatmentduration or alternatively to repeat the cycle. In the scale durationoption, the entire cycle is divided down in proportion to fit into anallotted time. Repeat cycle repeats the entire sequence by a fixednumber of cycles and reports the time required. Run/pause starts or holdthe procedure while Reset starts set up 301 over from scratch. Autosaverecord keeps a digital record of what procedures were performed, whenthey were performed and the new settings resulting from manualoverrides.

Once the program commences operation 304, the SPI bus writes the valuesof t_(on), φ and I_(LED) to the data registers within LED driver IC 207through SPI bus interface 210 b and SPI bus 213, docking of Clk θ andSync commence as generated from clock and timing circuit 210 e and LEDoperation implementing phototherapy waveform synthesis algorithms 330begins. As described previously, with each Sync pulse, updated values ofregister data are rewritten to the LED driver ICs according to thespecified algorithms, and any fault conditions are reported to thesystem and ultimately to the user.

LED Pad Design

Aside from its electronic control, the disclosed phototherapy apparatusincludes an aseptic flexible pad containing an array of LEDs illustratedin plan view in FIG. 26 and having an associated equivalent circuitschematic as shown. Pad 204 is formed using a material biochemicallyinert material such as Teflon or other non-porous non-reactivematerials, and containing embedded electronic components includingconnectors, wires or conductive interconnects, flexible andsemi-flexible PCBs (printed circuit boards), transistors, ICs, passivecomponents (such as resistors and capacitors), and LEDs.

The pad material may be homogeneous or comprise a softer interiormaterial with an impervious aseptic coating. To prevent biological crosscontamination among patients, the exterior of the pad should berelatively non-porous to avoid trapping bacteria, viral and microbialcontaminants, and should not be damaged by soap and water, phosphates,alcohol, low concentration acetic acid, commercial disinfectants, andother anti-bacterial agents. Without substantially diminishing its lightoutput, the pad should ideally completely enclose and contain its LEDswithin this bacterial barrier or coating material or otherwise form ahermetic seal with the LEDs protruding through the pad material. The padshould also preferably form a hermetic seal, bacterial and moisturebarrier with any connectors or wires protruding from the pad. Ifabsolute hermeticity is not possible, steps should be taken inmanufacturing to insure the best seal possible, especially to insuredelamination between the pad material and the extruding wires andcomponents is minimized by conditions used in molding or forming the paditself.

In one embodiment, pad 204 is divided into two pad portions, a largerpad portion 330 a comprising 16 rectilinearly arranged strings of LEDs332 a through 332 p and a smaller pad portion 330 b comprisingrectilinearly arranged 8 strings of LEDs 332 q through 332 x. Larger andsmaller pad portions 330 a and 330 b are fastened together mechanicallyat bendable seam 335 containing an electrical connection represented byconnector 331, The pad is designed to, when needed, wrap around apatient's appendage and optionally to secure the top of pad 330 b to thebottom of pad 330 a with mechanical fastener 336.

Mounted on a flexible or semi-flexible PCB. LED driver PCB 333 includesboth passive and semiconductor components including LED driver ICs 337 aand 337 b, and optionally microcontroller 338. In one embodiment, PCB333 is located within the end portion of larger pad portion 330 a nearfastener 336. Connector 334 electrically connects pad 204 to power andalternatively to LED driver circuitry not contained within LED driverPCB 333. Given that LED driver IC 333 is contained within larger LED pad320 a and LED strings 332 q through 332 x are contained within smallerpad portion 330 b, the cathodes of series-connected LED strings 205 qthrough 205 x are connected to LED driver PCB 333 through electricalconnector 331 while cathodes from LED strings 205 a through 205 p can beconnected without an intervening connector.

Electrically, each string as shown contains 12 series-connected LEDssharing a common anode and with cathodes separately connected to LEDdriver PCB 333. For example, LED string 332 a comprises the bottommostLED string on larger pad portion 330 a and has an equivalent circuitrepresented by 12 series-connected LEDs 205 a driven by a single channelon LED driver IC 337 a contained within LED driver PCB 333. Similarly,LED string 332 p comprises the topmost LED string on larger pad portion330 a and has an equivalent circuit represented by 12 series-connectedLEDs 205 p separately driven by a different channel on LED driver IC 337a. On smaller pad portion 330 b LED string 332 q has an equivalentcircuit represented by 12 series-connected LEDs 205 q driven by a singlechannel on an LED driver IC 337 b also contained within LED driver PCB333 and connected through electrical connector 331. Similarly, LEDdriver IC 337 b drives LED string 332 x with an equivalent circuitrepresented by 12 series-connected LEDs 205 x. Alternatively LED driverPCB 333 may be eliminated completely and the cathodes of all the LEDstrings connected directly to connector 334.

As shown in the embodiment of FIG. 26, each rectilinearly positioned LEDstring in the array comprises LEDs of substantially the same wavelengthλ, Ideally of similar brightness, where the wavelength of the LEDsvarious across the pad in some regular and periodic fashion. Forexample, LED strings 332 a, 332 d, 332 g, 332 j, 332 m, 332 p, 332 s,and 332 v comprise LEDs of wavelength λ₁, LED strings 332 b, 332 e, 332h, 332 k, 332 n, 332 q, 332 t, and 332 w comprise LEDs of wavelength λ₂,and LED strings 332 c, 332 f, 332 i, 332 l, 332 o, 332 r, 332 u, and 332x comprise LEDs of wavelength λ₃.

While the LEDs of the same wavelength are shown positioned in straightlines and arranged as rows, the LEDs may be distributed in otherpatterns, e.g. alternating the LED wavelengths along both row andcolumns in more complex patterns, where the layout of any given string332 cannot be represented as a straight line, but where the circuitconnection 205 still remains a simple series connection of 12 LEDs. Tofacilitate a more uniform distribution of the various wavelength LEDs, atwo layer flexible PCB or the use of conductive jumper may be requiredto electrically maintain a series connection of the same wavelengthLEDs. It is important LEDs of dissimilar wavelength should not be mixedinto the same series electrical connection or the ability to sequence orblend the brightness of dissimilar wavelengths of light will be lost.

To maintain flexible adjustment of the size of LED pad 204, small padportion 330 b can be removed from large pad portion 330 a andelectrically disconnected using connector 331 without disturbingoperation of the arrays of LEDs in large pad portion 330 a.Alternatively the pad may be designed to support a second small padportion (not shown) electrically connected to LED driver board 333through a second connector (not shown). In one embodiment, the secondsmall pad portion is physically attached to the large pad portion 330 aby a fastener at the bottom of large pad portion 330 a or by adaptingfaster 336 to support both configurations. In such instances theelectrical connector between the large pad portion 330 a and theoptional small pad portion containing the common anode connection andthe separate cathode connections driving the additional LED stringsshould not interfere with the function of electrical connector 334 usedto connect to power or drive electronics to pad 204.

In a second embodiment, the second small pad portion is physicallyattached to the large pad portion 330 a by a fastener located at the topof large pad portion 330 a. In such instance the common anode connectionand the separate cathode connections driving the additional LED stringsmust be routed to LED driver PCB 333 through smaller pad portion 330 brequiring a second electrical connector located at the top of smallerpad portion 330 b to connect to optional small portion pad 330 c, andrequiring double the pins on connector 331 to accommodate the additionalLED driver lines. For example without the ability to add optional smallpad portion 330 c, electrical connector 331 requires a minimum of 10pins-8 connector pins for LED cathode lines 205 q through 205 x andanother two for the common anode line and ground.

In the alternative embodiment with the expansion feature, theconnections need to drive the optional second small portion pad requires8 additional lines and to share the common anode and ground lines,increasing the number of pins needed in connector 331 by 9, i.e. from 10connector pins to 18 connector pins. As shown, LED driver IC drives 16LED strings from a single device. LED driver IC also includes separateoutputs, the addition of the second small pad portion as an extension toLED pad 204 requires no change in the electrical design or operation ofthe pad, except that the open LED connections should not trigger an openLED fault in LED driver IC 337 b. The fault setting register to avoidfalse open LED detect faults is user programmable in most LED driver ICsand can be controlled via microcontroller 209.

Although ground has no function in small pad portion 330 b and thesecond optional small pad portion, in an alternative embodiment, theground potential is used to bias an electrical shield throughout pad 204to comply with industry EMC (electromagnetic compatibility)specifications for controlling unwanted electromagnetic interference(EMI) during operation, especially when high-speed clocks are employedfor high bandwidth waveform synthesis. In single layer PCBs, the groundlayer can be used to bias conductors in all the PCB area not used bycarrying LED currents; in dual layer PCBs the second layer can be usedas a ground plane, greatly diminishing the radiated noise and providingEMI shielding, or in a 3-layer PCB, the front and backside layers bothbe grounded acting as a Faraday cage surrounding and encasing theconductors carrying LED currents, with the only openings in the frontside conductors open to accommodate mounting the LEDs. In anotherembodiment, a wire mesh comprising insulated wire is placed around asingle layer PCB with only the LEDs protruding beyond the mesh, wherebythe wire mesh is biased to ground to form a Faraday cage. The entireunit, including the PCB and wire mesh, is then molded with Teflon,whereby only LEDs protrude from pad 204.

The flexibility of LED pad 204 to conform to the topographic curvatureof the area receiving photoexcitation is important to avoid issuesconcerning poor light uniformity and varying penetration depthsproblematic with wands, torchlights, and stiff pads such as thoseillustrated in FIG. 4A and FIG. 4B. The benefit of the flexible andsemi-flexible pad is shown in FIG. 27, including flexible molding 382,e.g. comprising Teflon, flexible PCB 381, and flexible aseptic barrier385. Subdermal and epithelial tissue 37 and 36 naturally conform to thebody part requiring phototherapy, especially important for the uniformlyilluminating tissue on the arms, legs, or neck. By bending to conform tothe curvature of the treated area, LEDs 93 a through 93 e are able toadjust their radiated light pattern to be nearly perpendicular to thecurved surface of epithelial layer 36, resulting in a uniform brightnessand depth of penetration 384 in subdermal layer 37.

Notice that LED driver IC 86 and LEDs 93 a through 93 e compriserelatively stiff, i.e. inflexible plastic packages incapable ofsignificant bending. Because the surface area of the LEDs is small,minimal deformation is manifest so that no cracking or breakage resultsexcept for bending with an extremely tight radius of curvature. LEDdriver IC however is sufficiently large that package cracking is aconcern, mitigated in part by bending of the leads under stress, wherebythe leads act like a shock absorber to relieve stress from the plasticcavity. For this reason and others, LED driver IC should be packaged inleaded packages like the LQFP-packages where metallic leads extend fromthe package's exterior surface and bend down to the printed circuitboard. Because metallic leads, typically of copper, are able to bend,they relieve stress during deformation of the LED pad. To further reducethe magnitude of stress from bending and to reduce the risk of cracking.LED driver IC is mounted on the edge of flexible PCB 381 near the pad'sconnectors, or alternatively on a separate stiffer PCB, again locatednear a pad connector where bending is limited.

In contrast, leadless packages like the QFN where a small conductivearea on the underside of the package is soldered directly onto the PCBhave no means to bend and are therefore unable to absorb the stress ofdeformation without cracking the package or fracturing its solder jointto the PCB. For this reason and because leaded packages can be assembledusing low-cost wave soldering in older and cheaper PCB factories, leadedpackages are preferred in the disclosed phototherapy apparatus.

Depending on its application, an LED pad may include any number of LEDsand laser diodes configured in a variety of ways. While LED pad 204 isshown to comprise an array of three different wavelength LEDs, anynumber of wavelengths may be used in its construction. Instead of usingan array of three types of LED wavelengths as shown, the entire pad forexample may comprise an array of only a single wavelength LED, an arrayof two wavelengths of LEDs, or an array of four or more type of LEDs. Asshown in the graph of relative radiant intensity (%), a normalizedmeasure of an LED's optical power output, versus LED wavelength in FIG.28, LEDs may constitute a variety of wavelengths.

The power output curve for LED 342 has a mean value of 670 nm, and aspectral variation around its mean value of approximately ±10 nm. In theelectromagnetic spectrum, LED output 342 represents the lower frequencyend of visible light, dominated by a deep red color. Power output curve341 describes an LED in the near infrared spectrum, invisible to thehuman eye, having a nominal wavelength of 740 nm and a spectralvariation around its mean value of approximately ±15 nm. Power outputcurve 340 describes an LED deeper in the infrared spectrum, alsoinvisible to the human eye, having a nominal wavelength of 875 nm and aspectral variation around its mean value of approximately ±20 nm. OtherLEDs with wavelengths throughout the visible spectrum and into theultraviolet spectrum are also available as required.

The LEDs may be assembled separately into distinct packages, each withtheir own optical lens atop the package to better distribute the LED'slight output, or may be combined into a single package as a “tri-LED”device, preferably with separate anode and cathode contacts for each ofthe three LEDs. It is also possible for LED pads comprising multiple LEDarrays, laser diodes may in part be used in place of LEDs. As describedpreviously, the narrow spectral bandwidth produced laser diodes reducesthe observed magnitude of photobiomodulation with lasers compared toLEDs. For that reason, and because of their higher cost, their use islikely to remain restricted to specialty applications.

The total number of LEDs conducting at one time determines the averagebrightness, i.e. the optical power output, of the LED pad. Whilemultiple wavelengths of LED may be illuminated simultaneously, forreasons described previously in the application, it is generallybeneficial to drive only strings of LEDs having the same wavelengths atone time. Assuming that in most cases an array of only one LEDwavelength will be illuminated at one time and all with the samemagnitude of current I_(LED), then the total optical power output of anLED pad is given byP _(EMR) =k[m·n·I _(LED)/(# of types of LED wavelengths)]

For example LED pad 204 shown in FIG. 26 (including both large padportion 330 a and small pad portion 330 b) comprises 24 strings of LEDswith each string constructed from the series connection of 12 LEDs. Thetotal number of LEDs is therefore 288 or 96 LEDs in each array of anygiven wavelength. If the LEDs are biased at 20 mA at 100% duty factor,the LED array has an output power proportional to 96·20 mA=1.92LED-amps. Given the LED-amps and proportionality constant k, the actualoptical power output can be calculated. To determine the actual opticalpower output, however, requires knowing the LED optical power output ata given current, a parameter often not rated or specified on an LED'sdata sheet.

If, nonetheless, a higher areal power density (in W/cm²) is desired, theLEDs may be driven at a higher current, or a denser array of LEDs may beused. One other choice is to replace all the rows of single LEDs withtri-LEDs. In the example of LED pad 204 comprising LED pad portions 330a and 330 b, using tri-LEDs triples the areal power density butincreases the number of LED driver IC channels from 24 to 72 increasingthe number of 16-channel LED drivers from 2 to 5. It also increases thenumber of pins on connector 331 by 16, i.e. from 10 to 26 to accommodatethe added wiring.

As shown, pad 204 comprises 24 rows and 12 columns, i.e. where thenumber of LED driver IC channels n=24, and the number of LEDs connectedin series m=12. Alternatively, to increase the optical power output ofthe pad, the number of rows can be increased (by adding more LED driverIC channels), or the number of columns, i.e. the number of seriesconnected LEDs m, can be increased (but by increasing the supply voltageneeded to drive the LED strings. In a preferred embodiment, for safeoperation, the maximum number of series connected LED should be limitedso as to avoid requiring a supply voltage +V_(LED) exceeding 42V, anindustry recognized standard for safe low voltages and for UL approval.

LED Selection

To maximize the previously described photobiomodulation effect inphototherapy treatments of internal organs and tissue, the wavelength oflight emitted from a LED must penetrate the skin, passing through thebody to be absorbed by the targeted tissue of an internal organ ortissue. Numerous research laboratories have characterized the wavelengthabsorption data for various molecules within the human body, eachcontributing the spectral analysis from their specific works.

Collectively, the absorption spectra of various important bio-moleculesare summarized in FIG. 29A. The graph, covering the range in the visiblered and near infrared spectrum from 600 nm to 1100 nm, represents one ofthe few regions where non-ionizing EMR exhibits its greatest penetrationdepth in animals, mammals, and in humans. The graph illustrates inrelative magnitude of absorption, the absorption spectra for water (H₂O)in curve 341, for lipids and fats in curve 342, for oxygenatedhemoglobin (OxyHb) in curve 344, for deoxygenated hemoglobin (DeoxyHb)in curve 343. The absorption spectra of cytochrome-c oxidase (CCO), thebiochemical described previously as the cellular battery charger inmitochondria, is shown by curve 345 a and exhibiting a secondaryabsorption tail 345 b.

Using a relative absorption as a basis of comparison, water 341dominates the absorption spectra for wavelengths of 950 nm and longer,lipids and fats 342 dominate the absorption in a band of slightlyshorter wavelengths ranging from 900 to 950 nm. Below 750 nm,deoxygenated hemoglobin 343 in blood in the veinous system is thedominant bio-molecular absorber, absorbing EMR with an absorptioncoefficient more than four times that of oxygen rich blood in thearterial system.

Referring to FIG. 29B, the solid bold line 346 highlights the dominantbio-molecular absorbers in the human body, namely DeoxyHb 343 at shortwavelengths in the red portion of the visible light spectrum andespecially below 675 nm, and for lipids and water for longer infraredwavelengths from 900 nm to 1050 nm. At these wavelengths, the body isessentially opaque, preventing EMR from penetrating subdermal tissue toreach internal organs.

Bold line 346 clearly identifies that in between the absorption of waterin the infrared spectrum and of blood in the red visible spectrum, in aband from 675 nm to 900 nm, a transmission window 360 exists where lightcan penetrate the skin and reach internal organs. In the middle of thistransmission window, located in the range from 780 nm to 900 nm is theabsorption spectrum for cytochrome-c oxidase (CCO) 345 a, the dominantabsorber of light in mitochondria. So existing precisely in the middleof the frequency window where light can penetrate into and reach ananimal's internal organs, is the one band of frequencies wheremitochondria absorb light and where photoexcitation of cytochrome-coxidase produces energy.

Evolutionary biologists explain this fortuitous and remarkablycoincidental alignment of light's transmission window in animals and theabsorption spectra of CCO in mitochondria by symbiotic evolution, wheremitochondria (like their present day cousin blue-green algae), were oncefree floating organisms living in shallow water and deriving theirenergy from sunlight filtered by water. The fact that water absorbs orreflects ultraviolet and most visible light but passes infraredwavelengths provides indirect evidence of why mitochondria evolvedespecially to absorb light at infrared wavelengths. Later, aftermitochondria were incorporated into the first eukaryotic cells andultimately in animal and mammalian cells, evolutionary biologistspostulate that blood and specifically hemoglobin evolved symbioticallyso as to not block mitochondria's ability to absorb infrared light.While theology offers an alternative explanation, regardless of thereason, the fact remains that CCO in mitochondria absorbs light andinfrared radiation at precisely the wavelengths not blocked by water,fat and blood. Transmission window 360 therefore represents a spectralband where photobiomodulation of cells and tissue of internal organs hasits greatest absorption peak.

Photoexcitation using LEDs having wavelengths in this transmissionwindow exhibit good penetration depths unblocked by other biomolecules,and efficient absorption by CCO. Four bands of LED wavelengths are wellmatched to facilitating photoexcitation of mitochondrial CCO, namely 875nm, 819 nm, 740 nm, and 670 nm. Actually the secondary absorption tail345 b of CCO is partially blocked by DeoxyHb 343, reducing thepenetration of light at these wavelengths to one half or one third thatof the impinging light, and in general diminishing the photoexcitationresponse and photobiomodulation of internal organs at shorterwavelengths.

While the photoexcitation of CCO and the resulting creation of ATP arewell documented, it is not well understood at this time whether otherintracellular absorption mechanisms directly stimulatephotobiomodulation. It has been suggested, for example, that thecatalyst hydrogen peroxide (H₂O₂) may be formed directly throughphotoexcitation. Also in FIG. 29B, another small EMR transmission windowis present around 1080 nm. At this moment, no bio-molecules have beenidentified to absorb light at this wavelength so it remains unclearwhether any photobiomodulation will be manifested by illumination inthis window.

While the opportunity for photobiomodulation and phototherapy oninternal organs and subdermal tissue is restricted by the absorptionspectra of intervening blood, fat, water and other bio-molecules, thephotoexcitation of skin and surface layers is not. For photoexcitationon the skin's surface, the absorption spectrum 346 (shown as a dashedline) in FIG. 30 is not relevant because blood, fat and water arelocated beneath the affected tissue, and therefore cannot blockimpinging EM R. Unimpeded, EMR in the entire spectrum from 600 nm to1100 nm (including specifically 670 nm and 740 nm LEDs) is available forthe purpose of photoexcitation. Absorption of EMR on a surface, moreaccurately “adsorption”, over this range includes light is adsorbed byCCO 345 a, by CCO's secondary tail 345 b, by epidermis 347, and bymelanosomes (not shown). At present it remains unclear whether shorterwavelength light beyond red in the visible spectrum exhibitsphotobiomodulation or offers any phototherapeutic potential.

While ultraviolet light or UVL, primarily used for skin tanning, createsskin damage and can induce neoplasms (skin cancer), in low doses itoffers the potential for ridding the skin's surface of viral, yeast andbacterial invaders, in essence creating a hostile environ forinfections. In cases of gunshot, puncture wounds, skin lacerations,burns, and third degree bone breaks (where the skin is penetrated bybone) the use of ultraviolet LEDs in a sequential phototherapy regimencombined with red and infrared photoexcitation may assist in staving offinfection while stimulating an immune response and tissue repair, atleast temporarily until proper treatment in an aseptic environment canbe administered.

In conclusion, analysis of EMR absorption spectra suggests that longerwavelength LEDs in the 810 nm and 875 nm exhibit the potential forgreater photobiomodulation in internal organs while the entire spectrum,especially 670 nm and 740 nm LEDs are beneficial for photobiomodulationin skin and epithelial tissue. The disclosed phototherapy apparatusoffers a controlled means by which to drive and control LEDs and laserdiodes to maximize photobiomodulation in accordance with thisdisclosure.

I claim:
 1. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string, said algorithm specifying a frequency f₁ of pulses of EMR emitted by said plurality of LEDs, a duty factor of said pulses of EMR emitted by said plurality of LEDs and a magnitude of said current through said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 2. The phototherapy system of claim 1 wherein said algorithm further specifies a phase delay φ of said pulses of EMR emitted by said plurality of LEDs.
 3. The phototherapy system of claim 1 wherein said pad comprises a second LED string, said second LED string comprising a second plurality of LEDs adapted to generate EMR including radiation of a second wavelength λ₂, said process sequence being for controlling each of said first and second LED strings.
 4. The phototherapy system of claim 1 wherein said first channel driver comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; and a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register.
 5. The phototherapy system of claim 1 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 6. The phototherapy system of claim 1 wherein said living organism is a human being.
 7. The phototherapy system of claim 1 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 8. The phototherapy system of claim 1 wherein said first channel driver comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register; an I_(LED) register for storing data representing a magnitude of said electric current; and a digital-to-analog (D/A) converter, said D/A converter being coupled to said I_(LED) register, said D/A converter being coupled to a gate terminal of said MOSFET so as determine said magnitude of said electric current through said first LED string in response to said data stored in said I_(LED) register.
 9. The phototherapy system of claim 1 wherein said microcontroller comprises a clock and timing interface coupled to a counter for generating a clock pulse to advance said counter.
 10. The phototherapy system of claim 1 wherein said magnitude of said current through said first LED string specified in said algorithm is a constant magnitude.
 11. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string, said first channel driver comprising: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; and a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 12. The phototherapy system of claim 11 wherein said microcontroller comprises a clock and timing interface coupled to said counter for generating a clock pulse to advance said counter.
 13. The phototherapy system of claim 11 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 14. The phototherapy system of claim 11 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 15. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string, said first channel driver comprising: an I_(LED) register for storing data representing a magnitude of said electric current; a digital-to-analog (D/A) converter; and a MOSFET, said MOSFET being connected in series with said first LED string, said D/A converter being coupled to said I_(LED) register, said D/A converter being coupled to a gate terminal of said MOSFET so as determine said magnitude of said electric current in response to said data stored in said I_(LED) register; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 16. The phototherapy system of claim 15 wherein said first channel driver further comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; and a counter, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register.
 17. The phototherapy system of claim 15 wherein said first channel driver further comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; and a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register.
 18. The phototherapy system of claim 15 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 19. The phototherapy system of claim 15 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 20. The phototherapy system of claim 15 wherein said microcontroller comprises a clock and timing interface coupled to said counter for generating a clock pulse to advance said counter.
 21. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string, said algorithm specifying a frequency f₁ of pulses of EMR emitted by said plurality of LEDs, a phase delay φ of said pulses of EMR emitted by said plurality of LEDs and a magnitude of said current through said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 22. The phototherapy system of claim 21 wherein said pad comprises a second LED string, said second LED string comprising a second plurality of LEDs adapted to generate EMR including radiation of a second wavelength λ₂, said process sequence being for controlling each of said first and second LED strings.
 23. The phototherapy system of claim 21 wherein said first channel driver comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; and a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register.
 24. The phototherapy system of claim 21 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 25. The phototherapy system of claim 21 wherein said living organism is a human being.
 26. The phototherapy system of claim 21 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 27. The phototherapy system of claim 21 wherein said first channel driver comprises: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register; an I_(LED) register for storing data representing a magnitude of said electric current; and a digital-to-analog (D/A) converter, said D/A converter being coupled to said I_(LED) register, said D/A converter being coupled to a gate terminal of said MOSFET so as determine said magnitude of said electric current through said first LED string in response to said data stored in said I_(LED) register.
 28. The phototherapy system of claim 21 wherein said microcontroller comprises a clock and timing interface coupled to a counter for generating a clock pulse to advance said counter.
 29. The phototherapy system of claim 21 wherein said magnitude of said current through said first LED string specified in said algorithm is a constant magnitude.
 30. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string, said first channel driver comprising: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; and a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string, said algorithm specifying a frequency f₁ of pulses of EMR emitted by said plurality of LEDs and a magnitude of said current through said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 31. The phototherapy system of claim 30 wherein said pad comprises a second LED string, said second LED string comprising a second plurality of LEDs adapted to generate EMR including radiation of a second wavelength λ₂, said process sequence being for controlling each of said first and second LED strings.
 32. The phototherapy system of claim 30 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 33. The phototherapy system of claim 30 wherein said living organism is a human being.
 34. The phototherapy system of claim 30 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 35. The phototherapy system of claim 30 wherein said first channel driver further comprises: an I_(LED) register for storing data representing a magnitude of said electric current; and a digital-to-analog (D/A) converter, said D/A converter being coupled to said I_(LED) register, said D/A converter being coupled to a gate terminal of said MOSFET so as determine said magnitude of said electric current through said first LED string in response to said data stored in said I_(LED) register.
 36. The phototherapy system of claim 30 wherein said microcontroller comprises a clock and timing interface coupled to a counter for generating a clock pulse to advance said counter.
 37. The phototherapy system of claim 30 wherein said magnitude of said current through said first LED string specified in said algorithm is a constant magnitude.
 38. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string, said first channel driver comprising: a t_(on) register for storing data representing a length of time that said first LED string is turned on; a counter; a MOSFET, said MOSFET being connected in series with said first LED string, said counter being coupled to said t_(on) register, said counter being coupled to a gate terminal of said MOSFET so as to turn said MOSFET on for said length of time in response to said data stored in said t_(on) register; an I_(LED) register for storing data representing a magnitude of said electric current; and a digital-to-analog (D/A) converter, said D/A converter being coupled to said I_(LED) register, said D/A converter being coupled to a gate terminal of said MOSFET so as determine said magnitude of said electric current through said first LED string in response to said data stored in said I_(LED) register; a microcontroller comprising a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string, said algorithm specifying a frequency f₁ of pulses of EMR emitted by said plurality of LEDs and a magnitude of said current through said first LED string; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 39. The phototherapy system of claim 38 wherein said pad comprises a second LED string, said second LED string comprising a second plurality of LEDs adapted to generate EMR including radiation of a second wavelength λ₂, said process sequence being for controlling each of said first and second LED strings.
 40. The phototherapy system of claim 38 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 41. The phototherapy system of claim 38 wherein said living organism is a human being.
 42. The phototherapy system of claim 38 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 43. The phototherapy system of claim 38 wherein said microcontroller comprises a clock and timing interface coupled to a counter for generating a clock pulse to advance said counter.
 44. The phototherapy system of claim 38 wherein said magnitude of said current through said first LED string specified in said algorithm is a constant magnitude.
 45. A phototherapy system comprising: a first light-emitting diode (LED) string, said first LED string comprising a plurality of LEDs adapted to generate electromagnetic radiation (EMR) including radiation of a first wavelength λ₁; a first channel driver coupled to said first LED string for controlling an electric current through said first LED string; a microcontroller comprising: a pattern library, said pattern library storing at least one algorithm, said at least one algorithm defining a process sequence for controlling said first LED string, said algorithm specifying a frequency f₁ of pulses of EMR emitted by said plurality of LEDs and a magnitude of said current through said first LED string; and a clock and timing interface coupled to a counter for generating a clock pulse to advance said counter; and a pad comprising said first LED string, said first LED string being positioned in said pad so as to allow said EMR to be radiated into a living organism when said pad is positioned adjacent said living organism.
 46. The phototherapy system of claim 45 wherein said pad comprises a second LED string, said second LED string comprising a second plurality of LEDs adapted to generate EMR including radiation of a second wavelength λ₂, said process sequence being for controlling each of said first and second LED strings.
 47. The phototherapy system of claim 45 wherein said pad is flexible such that said pad can fit snugly against a curved surface of said living organism.
 48. The phototherapy system of claim 45 wherein said living organism is a human being.
 49. The phototherapy system of claim 45 wherein said EMR comprises a spectral band of wavelengths comprising said first wavelength λ₁.
 50. The phototherapy system of claim 45 wherein said magnitude of said current through said first LED string specified in said algorithm is a constant magnitude. 